FI92054C - Process for the preparation of 3- (o-methoxyphenoxy) -1,2-propanediol-1-carbamate - Google Patents

Process for the preparation of 3- (o-methoxyphenoxy) -1,2-propanediol-1-carbamate Download PDF

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Publication number
FI92054C
FI92054C FI891068A FI891068A FI92054C FI 92054 C FI92054 C FI 92054C FI 891068 A FI891068 A FI 891068A FI 891068 A FI891068 A FI 891068A FI 92054 C FI92054 C FI 92054C
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methoxyphenoxy
methyl
oxo
ether
propanediol
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FI891068A
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Finnish (fi)
Swedish (sv)
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FI891068A (en
FI891068A0 (en
FI92054B (en
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Manfred Mueller
Joachim Hess
Manfred Langer
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Boehringer Ingelheim Kg
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06—Esters of carbamic acids
    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C271/16—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Epoxy Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Description

9205492054

Menetelmå 3-(o-metoksifenoksi)-1,2-propaanidioli-l-kar- bamaatin valmistamiseksi - Forfarande for framstållning av 3- (o-metoxifenoxi)-1,2-propandiol-l-karbamat r 5 KeksinnSn kohteena on entistå parempi menetelmå 3-(o-metoksifenoksi) -1,2-propaanidioli-l-karbamaatin valmistamiseksi muodostamalla propyyliryhmån 2,3-asemassa substituoidusta propyyli (o-metoksifenyyli)eetteristå inertisså liuottimessa 4-t (o-metoksifenoksi)-metyyli]-2-okso-dioksolaania, joka 10 lohkaistaan ammoniakilla.The process for the preparation of 3- (o-methoxyphenoxy) -1,2-propanediol-1-carbamate - for the preparation of 3- (o-methoxyphenoxy) -1,2-propanediol-1-carbamate Process for the preparation of 3- (o-methoxyphenoxy) -1,2-propanediol-1-carbamate by forming a propyl group from a 2,3-substituted propyl (o-methoxyphenyl) ether in an inert solvent with 4-t (o-methoxyphenoxy) methyl] -2- oxo-dioxolane, which is cleaved with ammonia.

Metokarbamolia tiedetåån voitavan valmistaa siten, ettå guajakoli saatetaan reagoimaan 3-kloori-l,2-propaanidiolin kanssa, reaktiotuotteessa vaihdetaan pååteaseman OH-ryhmåt 15 klooriin fosgeenin vaikutuksen avulla ja kloorijohdos saatetaan reagoimaan ammoniakin kanssa (A. Kleemann, Pharmz. Wirkstoffe, 2. painos 81982), s. 578; US-PS 2 770 649).Methocarbamol is known to be prepared by reacting guaiacol with 3-chloro-1,2-propanediol, exchanging the OH groups of the terminal 15 for chlorine by the action of phosgene, and reacting the chlorine derivative with ammonia (A. Kleemann, Pharmz. 2. Wirkstoff, Wirkstoff). 81982), pp. 578; US-PS 2,770,649).

Saanto ei ole tåysin tyydyttåvå. f 20The yield is not entirely satisfactory. f 20

Nyttemmin on havaittu, ettå metokarbamolin synteesi voidaan edullisesti suorittaa seuraavan reaktiokaavion mukaisesti 1 ochj 25 °ch3 Ϊ : ^ 0~"V* (I) (II) (III) 30 OCH, 2. ϊIt has now been found that the synthesis of methocarbamol can advantageously be carried out according to the following reaction scheme: 1 ° H 25 ° ch 3 Ϊ: ^ 0 ~ "V * (I) (II) (III) 30 OCH, 2. ϊ

co. /Vc/o. / V

('s' OCHj-HC — CH,('s' OCHj-HC - CH,

' 111 -► I i J'111 -► I i J

Dabco \ /Dabco \ /

s Cs C

‘ II‘II

o 35 (IV) 92054 2 OCH, “» X.o 35 (IV) 92054 2 OCH, “» X.

>-OCH, — CH- CH, - O · CONH, 3- IV -* 'm (metokarbamoli)> -OCH, - CH- CH, - O · CONH, 3- IV - * 'm (methocarbamol)

Vaiheen 1 reaktio onnistuu hyvållå saannolla, kun yhdisteen I ja II annetaan reagoida vesipitoisessa alkalihydroksidi-10 liuoksessa (alkalihydroksidin ja guajakolin moolisuhde noin 1:1, epikloorihydriiniå ylimåårå) lisååmållå pieni måårå bentsyylitrietyyliammoniumkloridia. Tuloksena oleva 2,3-epoksipropyyli-2-metoksifenyylieetteri, sp. 31 - 33°C, voidaan saada hyvållå saannolla fraktiotislaamalla alipai-15 neessa.The reaction of Step 1 is accomplished in good yield by reacting Compounds I and II in aqueous alkali hydroxide-10 solution (molar ratio of alkali hydroxide to guaiacol about 1: 1, excess epichlorohydrin) by adding a small amount of benzyl chloride triethylammonium. The resulting 2,3-epoxypropyl-2-methoxyphenyl ether, m.p. 31-33 ° C, can be obtained in good yield by fractional distillation under reduced pressure.

Nyt on havaittu, ettå saattamalla saatu yhdiste reagoimaan hiilidioksidin kanssa korotetussa paineessa ja korotetussa låmpdtilassa katalyyttisen måårån 1,4-diatsabisyklo[2.2.2]-20 oktaania (Dabco) låsnåollessa pienesså mååråsså inerttiå liuotinta, esimerkiksi tolueenia, saadaan 4-[(o-metoksi-fenoksi)-metyyli]-2-oksodioksolonia hyvållå saannolla, kun kåytetåån 400 - 1000 kPa C02-painetta ja låmpdtilaa 110 - 160°C. mieluummin 120 - 140°C. Reaktio sujuu suhteel-25 lisen hitaasti. Sen jålkeen, kun hiilidioksidia on reagoi-• nut låhes teoreettinen måårå, lopetetaan reaktio.It has now been found that by reacting the obtained compound with carbon dioxide at elevated pressure and elevated temperature in the presence of a catalytic amount of 1,4-diazabicyclo [2.2.2] -20 octane (Dabco) in a small amount of an inert solvent, e.g. toluene, methoxy-phenoxy) -methyl] -2-oxodioxolone in good yield when a pressure of 400 to 1000 kPa CO2 and a temperature of 110 to 160 ° C are used. preferably 120-140 ° C. The reaction proceeds relatively slowly. After the carbon dioxide has reacted in an almost theoretical amount, the reaction is stopped.

4-[o-metoksifenoksi]-metyyli]-2-oksodioksolaanin lohkaisu suoritetaan ilman vålierotusta 26°C:ssa, edullisesti kåyt-30 tåmållå kaasumaista tai nestemåistå ammoniakkia.The cleavage of 4- [o-methoxyphenoxy] methyl] -2-oxodioxolane is carried out without intermediate separation at 26 ° C, preferably using gaseous or liquid ammonia.

Esimerkki .Example.

a) 2,3-epoksipropyyli-2-metoksifenyylieetteri : 35(a) 2,3-epoxypropyl-2-methoxyphenyl ether: 35

Liuos, joka sisåltåå 200 g (5 moolia) natriumhydroksidia 200 ml:ssa vettå, jååhdytetåån 10°C:een. 10 minuutin ku- 92054 3 luessa lisåtåån seos, jossa on 1300 g (14 moolia) epikloo-rihydriiniå, 620,7 g (5 moolia) guajakolia ja 6,3 g (0,028 moolia) bentsyylitrietyyliammoniumkloridia. Låmpo-tila nousee 80°C:een ja pidetåån tåmån jålkeen tunnin ajan 5 65°C:ssa. Huoneen låmpotilaan jååhdyttåmisen jålkeen liså tåån 100 ml dikloorimetaania ja saostunut natriumklorid! erotetaan imun avulla. Peståån kaksi kertaa 100 ml:11a dikloorimetaania ja orgaaninen faasi haihdutetaan alipai-neessa (2,5 kPa) ja 70°C haudelåmpdtilassa. Jåljelle jåånyt 10 oranssin vårinen oljy fraktioidaan 3 kPa paineessa ja 110°C:ssa, jolloin saadaan 633,6 g (70,3 %) otsikkoyhdis-tettå, sp. 31 - 33°C.A solution of 200 g (5 moles) of sodium hydroxide in 200 ml of water is cooled to 10 ° C. After 10 minutes, a mixture of 1300 g (14 moles) of epichlorohydrin, 620.7 g (5 moles) of guaiacol and 6.3 g (0.028 moles) of benzyltriethylammonium chloride is added. The temperature rises to 80 ° C and is then maintained at 5 65 ° C for one hour. After cooling to room temperature, add 100 ml of dichloromethane and precipitated sodium chloride! separated by suction. Wash twice with 100 ml of dichloromethane and evaporate the organic phase under reduced pressure (2.5 kPa) and at a bath temperature of 70 ° C. The remaining 10 orange oil is fractionated at 3 kPa and 110 ° C to give 633.6 g (70.3%) of the title compound, m.p. 31-33 ° C.

b) 3-(o-metoksifenoksi)-1,2-propaanidioli-l-karbamaatti 15 540,7 g (3 moolia) kohdan a) mukaisesti saatua yhdistettå ja 3,4 g (0,03 moolia) Dabco'a liuotetaan 125 ml:aan ksy-leeniå. Liuosta sekoitetaan 4 tuntia 130°C:ssa 650 kPa C02-paineessa ja sen jålkeen jååhdytetåån 24°C:een. Liså-20 tåån 2012 ml tolueenia, minkå jålkeen seokseen lisåtåån nestemåistå ammoniakkia, jolloin otsikkoyhdiste alkaa kiteytyå. Tunnin kuluttua lisåtåån 200 ml isopropyylialko-holia, kidepuuro liuotetaan 70°C:ssa ja sen jålkeen jååhdytetåån. Otsikkoyhdiste erotetaan imulla, peståån 300 ml :11a 25 tolueenia ja kuivataan.b) 3- (o-Methoxyphenoxy) -1,2-propanediol-1-carbamate 54040 g (3 moles) of the compound obtained in a) and 3.4 g (0.03 moles) of Dabco are dissolved in 125 ml to xylene. The solution is stirred for 4 hours at 130 ° C under a pressure of 650 kPa CO 2 and then cooled to 24 ° C. An additional 20 mL of toluene is added thereto, followed by the addition of liquid ammonia to the mixture, whereupon the title compound begins to crystallize. After 1 hour, 200 ml of isopropyl alcohol are added, the crystalline porridge is dissolved at 70 [deg.] C. and then cooled. The title compound is filtered off with suction, washed with 300 ml of toluene and dried.

• Saanto 674,8 (93 % teoreettisesta).• Yield 674.8 (93% of theory).

ff

Claims (1)

92ϋ54 Patenttivaatimus Menetelmå 3-(o-metoksifenoksi)-1,2-propaanidioli-l-kar-bamaatin valmistamiseksi muodostamalla propyyliryhmån 5 2,3-asemassa substituoidusta propyyli(o-metoksifenyyli)-eetteristå inertisså liuottimessa 4-[(o-metoksifenoksi)-metyyli]-2-okso-dioksolaania, joka lohkaistaan ammoniakil-la, tunnettu siitå, ettå dioksolaani muodostetaan saattamalla 2,3-epoksipropyyli(o-metoksifenyyli)eetteri 10 reagoimaan hiilidioksidin kanssa katalyyttisen måårån 1,4-diatsabisyklo(2.2.2)oktaania låsnåollessa C02-paineessa 400 - 1000 kPa låmpotilassa 110 - 160°C ja 4-[(o-metoksifenoksi) -metyyli]-2-okso-dioksolonin lohkaisu suoritetaan ilman vålierotusta låmpdtilassa alle 30°C kaasumaisella tai 15 nestemåisellå ammoniakilla. Forfarande ffir framstållning av 3-(o-metoxifenoxi)-1,2-20 propandiol-l-karbamat genom att av en i propylgruppen i 2,3-stållning substituerad propyl(o-metoxifenyl)eter i ett inert ldsningsmedel bilda 4-[ (o-metoxifenoxi)-metyl]-2-oxo-dioxolan, som avspjålks med ammoniak, kånneteck-n a t dårav, att dioxolanet bildas genom att omsåtta 25 2,3-epoxipropyl(o-metoxifenyl)eter med koldioxid i nårvaro .. av en katalytisk mångd 1,4-diazabicyklo (2.2.2) oktan i ett C02-tryck av 400 - 1000 kPa vid en temperatur av 110 - 160°C och 4-[ (o-metoxifenoxi)-metyl]-2-oxo-dioxo-lonens avspjålkning utfdrs utan mellanseparering vid en 30 temperatur under 30°C med ammoniak i gas- eller våtskeform. i92ϋ54 Patent Tivaatimus Menetelmå 3- (o-methoxyphenoxy) -1,2-propanidioli-1-carbamaatine valmistamisexi muodostamalla propyyliryhumane 2,3-asemass substituoidusta propyyli (o-methoxyphenyyli) etyethimethoxyamide -methyl] -2-oxo-dioxolaania, joka lohkaistaan ammoniaakilla, tunnettu siitå, one dioxolaani muodostetaan satattal 2,3-epoxypropylyl (o-methoxyphenyyli) ether 10 reagoimane hiilidioksidine octaania lock needle C02-paineessa 400 - 1000 kPa clamp potassium 110 - 160 ° C yes 4 - [(o-methoxyphenoxy) methyl] -2-oxo-dioxolonin lohkaisu suoritetaan ilman vaalierotusta lumpdtilassa all 30 ° C cheese mackerel tai 15 second. Process for the preparation of 3- (o-methoxyphenoxy) -1,2-20 propanediol-1-carbamate by forming a propyl (o-methoxyphenyl) ether substituted by an inert solvent substituted by the propyl group in 2,3 position. (o-methoxyphenoxy) methyl] -2-oxo-dioxolane, which is cleaved with ammonia, characterized in that the dioxolane is formed by reacting 2,3-epoxypropyl (o-methoxyphenyl) ether with carbon dioxide in the presence. of a catalytic amount of 1,4-diazabicyclo (2.2.2) octane at a CO 2 pressure of 400-1000 kPa at a temperature of 110-160 ° C and 4- [(o-methoxyphenoxy) methyl] -2-oxo The flushing of the dioxolone is carried out without intermediate separation at a temperature below 30 ° C with gas or liquid ammonia. in
FI891068A 1988-03-08 1989-03-07 Process for the preparation of 3- (o-methoxyphenoxy) -1,2-propanediol-1-carbamate FI92054C (en)

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DE19883807522 DE3807522C1 (en) 1988-03-08 1988-03-08
DE3807522 1988-03-08

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FI891068A FI891068A (en) 1989-09-09
FI92054B FI92054B (en) 1994-06-15
FI92054C true FI92054C (en) 1994-09-26

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5093456A (en) * 1989-06-14 1992-03-03 Minnesota Mining And Manufacturing Company Monocarbamate diols, polymers derived from them and nlo-active materials therefrom
ATE246182T1 (en) * 1997-05-12 2003-08-15 Daiso Co Ltd METHOD FOR PRODUCING 1,4-BENZODIOXANE DERIVATIVES
CN101838249B (en) * 2010-03-19 2015-08-19 浙江华海药业股份有限公司 A kind of method preparing high-purity guaiacol glycidyl ether
CN106349112A (en) * 2016-08-24 2017-01-25 浙江海洲制药有限公司 Preparation method of methocarbamol beta isomer
CN115043811A (en) * 2022-06-10 2022-09-13 苏州敬业医药化工有限公司 Preparation method of 4- [ (2-methoxyphenoxy) methyl ] -1, 3-dioxolane-2-one

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* Cited by examiner, † Cited by third party
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GB861960A (en) * 1957-01-22 1961-03-01 A H Robins Company Ltd Preparation of monocarbamates
DE1249852B (en) * 1964-10-07 1967-09-14 Dr Christian Brunnengraber Che mische Fabrik &. Co mbH Lübeck Process for the production of carbam acid esters from a glycermathers

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FI891068A (en) 1989-09-09
GB2216520A (en) 1989-10-11
DE3807522C1 (en) 1989-03-30
GB2216520B (en) 1991-06-26
FI891068A0 (en) 1989-03-07
GB8905218D0 (en) 1989-04-19
FI92054B (en) 1994-06-15
FR2628420A1 (en) 1989-09-15
FR2628420B1 (en) 1993-08-20

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