WO2022108833A1

WO2022108833A1 - Uv-leds photoreactor apparatus and associated methods

Info

Publication number: WO2022108833A1
Application number: PCT/US2021/059046
Authority: WO
Inventors: Pavlina HORAKOVA; Tomas Holas; Cvak LADISLAV; Eduard POLÁK
Original assignee: Teva Czech Industries S.R.O; Teva Pharmaceuticals Usa, Inc.
Priority date: 2020-11-17
Filing date: 2021-11-12
Publication date: 2022-05-27
Also published as: EP4247544A1

Abstract

Aspects of the present disclosure relate to a photoreactor apparatus comprising a reaction vessel; an intake configured to receive a reactant solution and supply the reactant solution to the reaction vessel, the reactant solution comprising lysergic acid or a salt, ester or derivative thereof; a light source, the light source comprising one or more light-emitting diodes, LEDs, configured to irradiate the interior of the reaction vessel, the one or more LEDs having a peak emission wavelength within the ultraviolet range; and an outlet configured to allow a reaction product to flow from the reaction vessel.

Description

UV-LEDS PHOTOREACTOR APPARATUS AND ASSOCIATED METHODS

BACKGROUND

[0001] The present technique relates to the field of photoreactors.

[0002] Photoreactors are apparatuses in which photochemical reactions are facilitated and performed, for example by way of a vessel to contain reactants and a light source to irradiate reactants in the vessel, in order to produce a reaction product. The photoreactor consumes power when in operation. As a system is scaled up to produce larger quantities of reaction product, the consumed power can become relatively large. Furthermore, the final reaction product may not be pure, but may exist in a mixture with contaminant impurities including products of reactions other than the desired reaction.

[0003] There is therefore a desire for improved photoreactors, with lower power consumption and reduced impurity quantity for a given photo-chemical reaction.

SUMMARY

[0004] At least some examples provide a photoreactor apparatus comprising: a reaction vessel; an intake configured to receive a reactant solution and supply the reactant solution to the reaction vessel, the reactant solution comprising lysergic acid or a salt, ester or derivative thereof; a light source, the light source comprising one or more light-emitting diodes, LEDs, configured to irradiate the interior of the reaction vessel, the one or more LEDs having a peak emission wavelength within the ultraviolet range; and an outlet configured to allow a reaction product to flow from the reaction vessel.

[0005] Further examples provide a method comprising: receiving a reactant solution into a reaction vessel, the reactant solution comprising lysergic acid or a salt, ester or derivative thereof; irradiating the reactant solution within the reaction vessel, said irradiating being performed by a light source comprising one or more light-emitting diodes, LEDs, having a peak emission wavelength within the ultraviolet range; and extracting a reaction product from the reaction vessel.

[0006] Further examples provide a system comprising: one or more photoreactor apparatuses as disclosed herein and/or claimed in any of the claims; a preparation apparatus configured to: produce a reactant solution comprising lysergic acid or a salt, ester or derivative thereof; and provide the reactant solution to an intake or intakes of said one or more photoreactor apparatuses, and a post-reaction apparatus configured to: receive a reaction product from an outlet or outlets of said one or more photoreactor apparatuses; and perform a post-reaction purification to purify the reaction product.

[0007] Further examples provide a light source comprising: a housing configured to transmit ultraviolet radiation; one or more light-emitting diodes, LEDs, disposed within the housing and having: a peak emission wavelength within the range of 350 nanometres to 380 nanometres; and negligible emission at wavelengths less than 325 nanometres, and a mounting for attachment to a photoreactor apparatus.

[0008] Further examples provide a photoreactor apparatus comprising: a reaction vessel; an intake configured to receive a reactant solution and supply the reactant solution to the reaction vessel; a light source, the light source comprising one or more light-emitting diodes, LEDs, configured to irradiate the interior of the reaction vessel, the one or more LEDs having a peak emission wavelength within the ultraviolet range; and an outlet configured to allow a reaction product to flow from the reaction vessel, wherein the light source is configured to provide a flux of more than 750 mW, and preferably more than 800 mW, at 25°C.

[0009] Further aspects, features and advantages of the present technique will be apparent from the following description of examples, which is to be read in conjunction with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

[0010] Figure 1 depicts an apparatus according to an example.

[0011] Figure 2 depicts a potential configuration of the apparatus of Figure 1.

[0012] Figure 3 shows two steps of a chemical process according to an example.

[0013] Figure 4 depicts an apparatus according to an example.

[0014] Figure 5 depicts a reaction vessel according to an example.

[0015] Figure 6 illustrates emission and absorption spectra of example light sources and reaction substances.

[0016] Figures 7A and 7B depict example flow modes which may be implemented in systems according to the present disclosure.

[0017] Figure 8 depicts a method according to an example.

DESCRIPTION OF EXAMPLES

[0018] A photoreactor apparatus according to an example of the present disclosure comprises a reaction vessel in which a photoreaction is to occur, and an intake configured to receive a reactant solution. In the present example, the reactant solution comprises lysergic acid or a salt, ester or derivative thereof. The reactant solution may for example comprise lysergic acid methylester (LAME). In this example, the reactant solution may also comprise lysergic acid.

[0019] The apparatus comprises a light source comprising one or more light-emitting diodes, LEDs, configured to irradiate the interior of the reaction vessel. The one or more LEDs have a peak emission wavelength within the ultraviolet range. The light source may for example be configured to facilitate the reaction by photomethoxylation of methylester of lysergic acid (LAME, an example reactant) to form LUME, as described in more detail below. The reaction may be a step of a wider process, for example to produce Nicergoline.

[0020] The apparatus further comprises an outlet configured to allow a reaction product (for example LUME) to flow from the reaction vessel.

[0021] The present apparatus provides significant advantages. For example, LEDs have a significantly lower power consumption and longer lifespan than many other photoreactor light sources (for example fluorescent tubes), and thus the present apparatus has a lower power consumption than comparative examples in which such alternative light sources are used. As an example, the time until a given LED has a 30% chance of burnout may be approximately 43000 hours when operated at a current of 500 mA.

[0022] Furthermore, LEDs can be configured to emit a relatively narrow wavelength range, corresponding to the desired reaction. This can improve the purity of the desired reaction product by reducing the incidence of other, undesired, reaction products. For example, if the desired reaction occurs when the reactant solution is irradiated with light at a given wavelength, and the undesired reaction producing the undesired product occurs when irradiated with light at a different wavelength, a light source with high intensity at the given wavelength and low intensity at other wavelengths will improve the purity of the reaction product. This can be achieved by way of an LED light source which emits light in a narrow range such that emission is high at the wavelength associated with the desired reaction and low at wavelengths associated with the undesired reaction.

[0023] A further advantage is that, provided that the LEDs are connected in parallel, failure of a single LED will not cause total failure of the apparatus but instead will merely cause a proportional reduction in the amount of light that is output. The apparatus can thus continue to operate.

[0024] Furthermore, the use of LEDs can avoid the use of hazardous materials, relative to comparative systems in which for example low pressure mercury lamps are used. The use of mercury in this manner may be restricted or otherwise undesirable, and the presently disclosed use of LEDs averts this.

[0025] In an example, the LEDs have a peak emission wavelength within the range of 350 nanometres, nm, to 380 nm. The emission may be negligible at wavelengths less than 325 nm or, preferably, negligible at wavelengths less than 340 nm. This can reduce the impurity quantity. In particular, in the case of photomethoxylation of LAME to form LUME, this can significantly reduce the production of the undesirable DHLAME impurity (as described in more detail below). One skilled in the art will appreciate that “negligible” means a value that is functionally equivalent to zero, or can be considered as zero for practical purposes. For example, the value may be so close to zero as to cause no measurable effect, or to not be measurably distinct from zero.

[0026] In an example, the apparatus comprises a flow controller configured to circulate the reactant solution through the reaction vessel. The flow controller may repeatedly circulate the reactant solution, in order to increase the amount of time for which the solution is exposed to the light from the light source. Alternatively, the flow controller may circulate the reactant solution only once through the reaction vessel. This efficiently allows a continuous production of the reaction product, as opposed to repeatedly circulating a single batch of reactant solution, before extracting that batch and repeating with further batches.

[0027] In the example in which the flow controller repeatedly circulates the reactant solution, the apparatus may comprise a reaction product analysis unit configured to measure an amount or concentration of the reaction product and, responsive to the amount or concentration exceeding a threshold, cause the outlet to allow the reaction product to flow from the reaction vessel. The reactant solution can thus be circulated until a desired concentration of reaction product is achieved, after which the reaction product is extracted. The final concentration of reaction product can thus be effectively controlled.

[0028] In an example, the apparatus comprises a flow controller configured to control a flow rate, for example a predefined flow rate, of the reaction solution from the intake to the outlet. The apparatus may further comprise a reaction product analysis unit configured to measure an amount or concentration of the reaction product at the outlet, wherein the flow controller is configured to control the flow rate based on the measured amount or concentration and a target amount or concentration. The flow rate can thus be controlled so that reaction product at the outlet has the target concentration. This allows the output concentration to be controlled even in the example in which the reactant solution is only passed a single time through the reaction vessel such that reaction product is continually produced. [0029] In an example, the light source is disposed within a housing, said housing being configured to contain an inertisation agent such as an inert gas, for example gaseous nitrogen or argon. This can prolong the lifespan of the light source, by preventing reactive agents from coming into contact therewith. The housing may comprise a UV-transparent material such as quartz glass, to allow the emitted light to enter the reaction vessel and thereby irradiate the reactant solution.

[0030] The apparatus may comprise a cooling system configured to cool the one or more LEDs, for example a water cooling system or other cooling system. This can improve the efficiency of operation of the LED light source.

[0031] The apparatus may comprise an LED controller configured to control an output power of the one or more LEDs by pulse width modulation. This allows the intensity of output light to be controlled, for example as a trade-off between energy consumption and reaction rate. Furthermore, some LEDs decrease in light intensity over time. This can be compensated by controlling the output power. This may for example be automatically performed by the apparatus.

[0032] In an example of the present disclosure, which may for example be implemented using the above-described example apparatus, there is provided a method comprising receiving a reactant solution into a reaction vessel, the reactant solution comprising lysergic acid or a salt, ester or derivative thereof. The reactant solution may comprise lysergic acid methylester (LAME). The reactant solution is then irradiated within the reaction vessel, said irradiating being performed by a light source comprising one or more light-emitting diodes, LEDs, having a peak emission wavelength within the ultraviolet range. The reaction product is then extracted from the reaction vessel. The reaction product may be a compound of the formula depicted below, or a salt, ester or derivative thereof, for example a methylester thereof

[0033] In a further example, there is provided a system comprising one or more photoreactor apparatuses as set out above. The system further comprises a preparation apparatus configured to produce a reactant solution comprising lysergic acid or a salt, ester or derivative thereof, and to provide the reactant solution to an intake or intakes of said one or more photoreactor apparatuses. The system additionally comprises a post-reaction apparatus configured to receive a reaction product from an outlet or outlets of said one or more photoreactor apparatuses, and to perform a post-reaction purification to purify the reaction product.

[0034] The one or more photoreactor apparatus may comprise a plurality of photoreactor apparatuses arranged in parallel, or in series, or a combination thereof. A parallel arrangement allows the quantity of reaction product to be increased by simultaneously operation of the parallel apparatuses. A serial arrangement allows the output of one apparatus to be provided as the input to the next apparatus, thereby increasing the final quantity of reaction product.

[0035] In an example, there is provided a light source, which may for example be configured to operate within a photoreactor apparatus as set out above. The light source may comprise a housing configured to transmit ultraviolet radiation, or a housing may be provided by a photoreactor apparatus in which the light source is installed. The light source further comprises one or more LEDs disposed within the housing and having a peak emission wavelength within the range of 350 nanometres to 380 nanometres, and negligible emission at wavelengths less than 325 nanometres. This may be optimised to increase the reaction rate of LAME into LUME, whilst reducing the reaction of LUME into DHLUME, as described in more detail below. The light source further comprises a mounting for attachment to a photoreactor apparatus such as those described above.

[0036] In a further example, there is provided a photoreactor apparatus comprising a reaction vessel, an intake configured to receive a reactant solution and supply the reactant solution to the reaction vessel, a light source, and an outlet configured to allow a reaction product to flow from the reaction vessel. The light source comprises one or more light-emitting diodes, LEDs, configured to irradiate the interior of the reaction vessel, the one or more LEDs having a peak emission wavelength within the ultraviolet range. The light source is configured to provide a flux of more than 750 mW, and preferably more than 800 mW, at 25°C. The use of such a high-power light source can facilitate reaction rates significantly higher than those achieved by comparative examples in which a lower power light source is used.

[0037] Examples of the present disclosure will now be described with reference to the drawings.

[0038] Figure 1 schematically shows a photoreactor apparatus 100 according to an example of the present disclosure. [0039] The photoreactor apparatus comprises a reaction vessel 105. The reaction vessel has an intake 110, into which a reactant solution is received. In the present example, as described in more detail elsewhere herein, the reactant solution comprises lysergic acid or a salt, ester or derivative thereof. However, in other examples the reactant solution may comprise additional or alternative ingredients.

[0040] The apparatus 105 comprises a light source 115. The light source 115 comprises one or more light-emitting diodes, LEDs, 120 configured to irradiate the interior of the reaction vessel. The LEDs 120 have a wavelength that is determined based on a desired reaction product to be produced from the reactant solution. In the present example, the LEDs have a peak emission wavelength in the ultraviolet, UV, range in order to cause the reaction of the aforementioned lysergic acid, which may be in the form of lysergic acid methylester, LAME) into LUME as described in more detail below.

[0041] The reactant solution travels through the reaction vessel 105 and is thereby irradiated by UV light from the LEDs 120 to produce the reaction product. The apparatus 100 has an outlet 125 configured to allow a reaction product to flow from the reaction vessel.

[0042] Figure 2 shows one potential configuration 200 of the apparatus 100 of Figure 1. In this example, the reaction vessel 205 has a cylindrical shape, with an intake pipe 210 near the base and an outlet pipe 225 near the top. The reactant solution may for example be pumped through the reaction vessel 205 from the intake 210 to the outlet 225 by a pump (not shown).

[0043] The light source 215 is located within a cylindrical housing in the centre of the cylindrical reaction vessel 205. This configuration allows the LEDs to efficiently irradiate the reactant solution in a full 360 degrees about the longitudinal axis. The light source 215 may be configured such that the LEDs and accompanying circuitry can be removed from the reaction vessel, for example for repair or replacement. For example, the light source 215 may be removably positioned within a cavity. The cavity may extend through the whole body of the reaction vessel 205 and thereby allow access from both ends of the reaction vessel 205. Cooling of the light source 215 can thus be improved.

[0044] As mentioned above, one use of the above-described apparatus is to convert lysergic acid methylester, LAME, by photomethoxylation into LUME. Structural formulas for LAME (formula I) and LUME (formula II) follow:

LAME

LUME

[0045] Figure 3 shows two steps of a process for producing LUME. A specific example of how this process can be performed will now be described, but one skilled in the art will appreciate that other methods for performing the illustrated reaction also fall within the scope of the present disclosure.

[0046] In an example of the first step of Figure 3, the synthesis starts with the dissolution of lysergic acid, LA, in 5% methanolic solution of sulfuric acid, H2SO4, to produce LAME. In an example of the second step of Figure 3, the LAME is then irradiated in a photoreactor according to the present disclosure. The irradiation may for example be performed for an average duration of 35 hours. The irradiation causes photomethoxylation of the LAME, to produce LUME. Figure 3 also shows two potential configurations of DHLAME, an undesirable impurity in the reaction product which is produced by irradiation of LUME. Examples of the present disclosure provide reduced production of DHLAME, as described in more detail below. [0047] The LUME is then isolated (not represented in Figure 3). This can be performed by neutralising the acidic reaction mixture by ammonia gas, or another base such as potassium carbonate, and treating the reaction mixture with activated charcoal. The neutralised and treated reaction mixture is then thickened by distillation to approximately one third of its prior volume. After this, the distillation residue is treated with toluene, aqueous ammonia solution and water. When the water is added, the mixture is immediately cooled to 0-5°C. When it reaches this temperature, it is allowed to crystallize for 4 hours. The solids are then centrifuged off and washed with the mixture of water and toluene, thereby leading to relatively pure LUME.

[0048] Further steps may then be performed to produce a final product such as Nicergoline from the LUME. In an example, these further steps include methylation on the nitrogen of the indol cyclus to obtain MeLUME, which esteric group is subsequently reduced on primal alcohol (MeLUOL). Finally, Nicergoline is produced by reaction of MeLUOL with 5- bromonicotinic acid chloride.

[0049] Figure 4 shows an apparatus 400 for production of LUME, according to an example of the present disclosure. The apparatus 400 comprises a reaction vessel 405, which may for example be the reaction vessel of Figure 1 or Figure 2. Within the reaction vessel 405 is a light source apparatus 415 comprising four LED arrays 420 on each side of the light source apparatus 415, for a total of sixteen arrays, and an LED driver 423. The light source apparatus 415 is located in an inert atmosphere, for example nitrogen gas, contained within a UV-transparent quartz glass housing 425. This prevents penetration of humidity, and also prevents penetration of reactant solution and/or reaction product within the LEDs, which could cause damage. The reaction vessel 405 may further comprise a UV-safe external housing, to protect workers or bystanders from exposure to residual UV radiation. The housing may also be configured to be explosion-safe.

[0050] The apparatus 400 comprises a LAME source 430. The LAME may be provided to the LAME source from a pre-reaction unit 435, which may for example produce the LAME from LA as described above in relation to Figure 3. The LAME is pumped from the LAME source 430 to an intake of the reaction vessel 405 by a pump 440. The LAME is pumped through the reaction vessel, within which it is at least partially converted by photomethoxylation to LUME. The reaction product is then pumped out of an outlet of the reaction vessel 405 to a UV spectrometer 445.

[0051] The UV spectrometer 445 analyses the LUME content in the reaction product. Based on this analysis, the speed of the pump 440 may be adjusted. For example, if the LUME content is lower than a threshold, the pump 440 may be slowed so that a given quantum of LAME spends more time in the reaction vessel 405, thereby increasing the content of LUME that is produced from a given quantity of LAME. Conversely, if the LUME content is higher than the threshold, the pump speed may be increased, thereby increasing the quantity of LAME which is pumped through the reaction vessel 405 in a given time period. The pump speed can thus be optimised, for example to maximise LUME production. [0052] Alternatively or additionally, the reaction rate can be controlled by controlling the output power of the LED arrays 420. This may for example be performed by varying the current provided to the LEDs, either by linearly varying the supplied current or by applying pulsewidth modulation.

[0053] The LUME product 450 (along with impurities) is then collected. The product may, in some examples, be returned to the LAME source 430 for recirculation through the reaction vessel 405. Post-reaction steps may be performed at a post-reaction unit 455, for example to isolate and purify the LUME and subsequently produce Nicergoline (as explained above in relation to Figure 3).

[0054] Whilst the LED arrays 420 are more energy efficient than, for example, fluorescent tubes, they still produce heat and can thus become damaged. To mitigate this, the light source apparatus 415 is water cooled. Water is circulated via pipe 460 to cooling apparatus 465 which may for example comprise a thermostat to ensure that a desired temperature is maintained. The light source apparatus 415 may also comprise a thermo detector 470 to monitor the temperature thereof and thereby adjust the water cooling. The lifespan of the LED arrays 420 is thus improved.

[0055] Figure 5 depicts a more detailed representation of a reaction vessel 505, which may for example be used in the systems of Figures 1, 2 and 4. The reaction vessel 505 comprises an inlet 510 for receiving a reactant solution, and an outlet 525 for outputting a reaction product. The reaction vessel 505 further comprises a cavity 530 into which a light source apparatus can be inserted.

[0056] The reaction vessel 505 further comprises a helical mixer. However, other implementations do not implement such a mixer.

[0057] Figure 6 depicts example emission spectra of a presently disclosed LED light source and a comparative example of a mercury lamp. It can be seen that the LED spectrum has a narrower emission peak than that of the mercury lamp. Specifically, the emission is low at wavelengths outside the range of 350 - 380 nm (nanometres), and is negligible below 340 nm. [0058] Figure 6 further depicts absorption spectra of LAME and LUME. As noted above, LUME is produced by UV photoreaction of LAME. However, the undesirable DHLAME impurity is produced by further UV photoreaction of LUME.

[0059] It can be seen from Figure 6 that the mercury lamp emission peak overlaps with the rightmost LUME absorption peak. Thus, comparative examples in which mercury lamps are used will cause some of the produced LUME to be converted to DHLAME. [0060] Conversely, it can also be seen from Figure 6 that whilst the LED emission peak overlaps with the rightmost LAME absorption peak (and thus will cause production of LUME), it has negligible overlap with the LUME absorption spectrum. In particular, the LED has negligible emission at wavelengths below 340 nm, and LUME has negligible absorption of light with wavelengths above 325 nm. An LED light source according to the present disclosure can thus be used to produce LUME, with only a negligible quantity (if any) of the produced LUME being further converted to DHLAME.

[0061] It can be seen that the LED emission spectrum has a smaller overlap with the LAME absorption spectrum than the mercury lamp emission spectrum. However, LEDs according to the present disclosure can be configured to have a radiometric power around 130 times greater than that of a comparative mercury lamp. For example, the LED light source may advantageously be configured to provide a flux of more than 750 milliwatts (mW) or, even more advantageously, a flux of more than 800 mW. Systems according to the present disclosure can thus produce a satisfactory yield, which may for example be comparable to that of a comparative system incorporating a mercury lamp.

[0062] More specifically, the LED light source may be configured to provide a radiometric flux of between 810 mW and 857 mW at 25°C and a peak emission wavelength of 365 nm (as measured within 1-2 cm of the LED lens).

[0063] Figures 7A and 7B schematically depict two flow modes which may be implemented within the present disclosure. Each of these figures depicts a photoreactor vessel 705 configured as described elsewhere in the present disclosure.

[0064] In the mode depicted in Figure 7A, reactant solution is provided from a source 710, and circulated through the photoreactor 705 until a desired concentration of reaction product has been produced. This allows production of batches of reaction product.

[0065] Conversely, in the mode depicted in Figure 7B, a reactant solution is provided from a source 715 and passed a single time through to the photoreactor 705 to an output 720. The output concentration of reaction product can be varied by adjusting the flow rate through the photoreactor (for example as described in more detail above in relation to Figure 4). This allows continuous production of reaction product.

[0066] Both flow modes therefore allow for control of the reaction rate, for example to produce a desired quantity of reaction product within a desired time or with a desired efficiency. [0067] In some systems, multiple photoreactors 705 are provided. These may be connected in series or in parallel, using either of the above-described flow modes. The system can thus be effectively scaled to increased production capacities. [0068] Figure 8 illustrates a method according to an example of the present disclosure. The method may for example be performed by a photoreactor apparatus as described elsewhere herein.

[0069] At step 805, reactant solution is received into a reaction vessel. The reactant solution comprises lysergic acid or a salt, ester or derivative thereof.

[0070] At step 810, the reactant solution is irradiated within the reaction vessel. The irradiation is performed by a light source comprising one or more LEDs having a peak emission wavelength within the UV range.

[0071] At step 815, a reaction product is extracted from the reaction vessel.

[0072] Apparatuses and methods are thus provided for the provision and use of photoreactor apparatus and light sources therein.

[0073] From the above description it will be seen that the techniques described herein provides a number of significant benefits. In particular, systems according to the present disclosure provide improved efficiency and reliability of operation, and improved purity of reaction products.

[0074] In the present application, the words “configured to...” are used to mean that an element of an apparatus has a configuration able to carry out the defined operation. In this context, a “configuration” means an arrangement or manner of interconnection of hardware or software. For example, the apparatus may have dedicated hardware which provides the defined operation, or a processor or other processing device may be programmed to perform the function. “Configured to” does not imply that the apparatus element needs to be changed in any way in order to provide the defined operation.

[0075] Although illustrative embodiments of the invention have been described in detail herein with reference to the accompanying drawings, it is to be understood that the invention is not limited to those precise embodiments, and that various changes and modifications can be effected therein by one skilled in the art without departing from the scope of the invention as defined by the appended claims.

Claims

WE CLAIM:

1. A photoreactor apparatus comprising: a reaction vessel; an intake configured to receive a reactant solution and supply the reactant solution to the reaction vessel, the reactant solution comprising lysergic acid or a salt, ester or derivative thereof; a light source, the light source comprising one or more light-emitting diodes, LEDs, configured to irradiate the interior of the reaction vessel, the one or more LEDs having a peak emission wavelength within the ultraviolet range; and an outlet configured to allow a reaction product to flow from the reaction vessel.

2. An apparatus according to any preceding claim, wherein said one or more LEDs have a peak emission wavelength within the range of 350 nanometres to 380 nanometres.

3. An apparatus according to claim 2, wherein said one or more LEDs have negligible emission at wavelengths less than 325 nanometres, and preferably have negligible emission at wavelengths less than 340 nanometres.

4. An apparatus according to any preceding claim, comprising a flow controller configured to circulate the reactant solution through the reaction vessel.

5. An apparatus according to claim 4, wherein the flow controller is configured to repeatedly circulate the reactant solution through the reaction vessel, the apparatus comprising a reaction product analysis unit configured to: measure an amount or concentration of the reaction product; and responsive to the amount or concentration exceeding a threshold, cause the outlet to allow the reaction product to flow from the reaction vessel.

6. An apparatus according to any of claims 1 to 3, comprising a flow controller configured to control a flow rate of the reaction solution from the intake to the outlet.

7. An apparatus according to claim 6, wherein the flow rate is a predefined flow rate.

8. An apparatus according to claim 6, comprising a reaction product analysis unit configured to measure an amount or concentration of the reaction product at the outlet, wherein the flow controller is configured to control the flow rate based on the measured amount or concentration and a target amount or concentration.

9. An apparatus according to any preceding claim, wherein the light source is disposed within a housing, said housing being configured to contain an inertisation agent.

10. An apparatus according to claim 9, wherein the inertisation agent is an inert gas, the inert gas optionally being gaseous nitrogen.

11. An apparatus according to claim 9 or claim 10, wherein the housing comprises an ultraviolent-transparent material .

12. An apparatus according to any preceding claim, comprising a cooling system configured to cool said one or more LEDs, said cooling system optionally being a water cooling system.

13. An apparatus according to any preceding claim, comprising an LED controller configured to control an output power of said one or more LEDs by pulse width modulation.

14. A method compri sing : receiving a reactant solution into a reaction vessel, the reactant solution comprising lysergic acid or a salt, ester or derivative thereof; irradiating the reactant solution within the reaction vessel, said irradiating being performed by a light source comprising one or more light-emitting diodes, LEDs, having a peak emission wavelength within the ultraviolet range; and extracting a reaction product from the reaction vessel.

15. A method according to claim 14, wherein the reactant solution comprises lysergic acid methylester, LAME. 15

16. A method according to claim 14 or claim 15, wherein the reaction product is a compound of formula (II) or a salt, ester or derivative thereof, said reaction product optionally being a methylester thereof.

17. A system comprising: one or more photoreactor apparatuses as claimed in any of claims 1 to 13; a preparation apparatus configured to: produce a reactant solution comprising lysergic acid or a salt, ester or derivative thereof; and provide the reactant solution to an intake or intakes of said one or more photoreactor apparatuses, and a post-reaction apparatus configured to: receive a reaction product from an outlet or outlets of said one or more photoreactor apparatuses; and perform a post-reaction purification to purify the reaction product.

18. A system according to claim 17, wherein said one or more photoreactor apparatuses comprises a plurality of photoreactor apparatuses arranged in parallel.

19. A system according to claim 17, wherein said one or more photoreactor apparatuses comprises a plurality of photoreactor apparatuses arranged in series.

20. A light source comprising: one or more light-emitting diodes, LEDs, disposed within a housing and having: a peak emission wavelength within the range of 350 nanometres to 380 nanometres; and negligible emission at wavelengths less than 325 nanometres, and a mounting for attachment to a photoreactor apparatus.

21. A photoreactor apparatus comprising: a reaction vessel; an intake configured to receive a reactant solution and supply the reactant solution to the reaction vessel; 16 a light source, the light source comprising one or more light-emitting diodes, LEDs, configured to irradiate the interior of the reaction vessel, the one or more LEDs having a peak emission wavelength within the ultraviolet range; and an outlet configured to allow a reaction product to flow from the reaction vessel, wherein the light source is configured to provide a flux of more than 750 mW, and preferably more than 800 mW, at 25°C.