GB2430433A - Preparation & purification of 1-[4-(4-benzyloxy)phenyl]-2-(4-benzylpiperidin-1-yl)-1-propanone, & use thereof in stereospecific preparation of ifenprodil - Google Patents
Preparation & purification of 1-[4-(4-benzyloxy)phenyl]-2-(4-benzylpiperidin-1-yl)-1-propanone, & use thereof in stereospecific preparation of ifenprodil Download PDFInfo
- Publication number
- GB2430433A GB2430433A GB0519275A GB0519275A GB2430433A GB 2430433 A GB2430433 A GB 2430433A GB 0519275 A GB0519275 A GB 0519275A GB 0519275 A GB0519275 A GB 0519275A GB 2430433 A GB2430433 A GB 2430433A
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- United Kingdom
- Prior art keywords
- ifenprodil
- preparation
- process according
- benzyloxy
- give
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- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 229960003998 ifenprodil Drugs 0.000 title claims abstract description 17
- 238000000746 purification Methods 0.000 title claims description 5
- 238000002360 preparation method Methods 0.000 title abstract 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 title abstract 2
- UYNVMODNBIQBMV-UHFFFAOYSA-N 4-[1-hydroxy-2-[4-(phenylmethyl)-1-piperidinyl]propyl]phenol Chemical compound C1CC(CC=2C=CC=CC=2)CCN1C(C)C(O)C1=CC=C(O)C=C1 UYNVMODNBIQBMV-UHFFFAOYSA-N 0.000 title description 6
- 230000000707 stereoselective effect Effects 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract description 19
- RARSHUDCJQSEFJ-UHFFFAOYSA-N p-Hydroxypropiophenone Chemical compound CCC(=O)C1=CC=C(O)C=C1 RARSHUDCJQSEFJ-UHFFFAOYSA-N 0.000 claims abstract description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 9
- 230000031709 bromination Effects 0.000 claims abstract description 6
- 238000005893 bromination reaction Methods 0.000 claims abstract description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims abstract 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims abstract 4
- 239000002904 solvent Substances 0.000 claims abstract 3
- 238000001953 recrystallisation Methods 0.000 claims abstract 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 19
- 238000004519 manufacturing process Methods 0.000 claims description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 8
- JQRYUMGHOUYJFW-UHFFFAOYSA-N pyridine;trihydrobromide Chemical compound [Br-].[Br-].[Br-].C1=CC=[NH+]C=C1.C1=CC=[NH+]C=C1.C1=CC=[NH+]C=C1 JQRYUMGHOUYJFW-UHFFFAOYSA-N 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 2
- KZKRRZFCAYOXQE-UHFFFAOYSA-N 1$l^{2}-azinane Chemical group C1CC[N]CC1 KZKRRZFCAYOXQE-UHFFFAOYSA-N 0.000 claims 1
- IKFGSOJYHVTNDV-UHFFFAOYSA-N 1-(4-phenylmethoxyphenyl)propan-1-one Chemical compound C1=CC(C(=O)CC)=CC=C1OCC1=CC=CC=C1 IKFGSOJYHVTNDV-UHFFFAOYSA-N 0.000 claims 1
- 239000007858 starting material Substances 0.000 claims 1
- 238000005804 alkylation reaction Methods 0.000 abstract description 4
- 238000005574 benzylation reaction Methods 0.000 abstract description 4
- ABGXADJDTPFFSZ-UHFFFAOYSA-N 4-benzylpiperidine Chemical compound C=1C=CC=CC=1CC1CCNCC1 ABGXADJDTPFFSZ-UHFFFAOYSA-N 0.000 abstract description 3
- 230000029936 alkylation Effects 0.000 abstract description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 abstract description 2
- 230000003197 catalytic effect Effects 0.000 abstract description 2
- 238000001816 cooling Methods 0.000 abstract description 2
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 2
- 239000001257 hydrogen Substances 0.000 abstract description 2
- 239000012280 lithium aluminium hydride Substances 0.000 abstract description 2
- 239000002002 slurry Substances 0.000 abstract description 2
- 239000012279 sodium borohydride Substances 0.000 abstract description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 abstract description 2
- 239000000543 intermediate Substances 0.000 abstract 8
- -1 benzyl halide Chemical class 0.000 abstract 1
- 238000001704 evaporation Methods 0.000 abstract 1
- 230000008020 evaporation Effects 0.000 abstract 1
- 238000007711 solidification Methods 0.000 abstract 1
- 230000008023 solidification Effects 0.000 abstract 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 5
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000008186 active pharmaceutical agent Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229940088679 drug related substance Drugs 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 229940082496 Adrenoreceptor antagonist Drugs 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 2
- 230000004968 inflammatory condition Effects 0.000 description 2
- QWXYZCJEXYQNEI-OSZHWHEXSA-N intermediate I Chemical compound COC(=O)[C@@]1(C=O)[C@H]2CC=[N+](C\C2=C\C)CCc2c1[nH]c1ccccc21 QWXYZCJEXYQNEI-OSZHWHEXSA-N 0.000 description 2
- 229960004592 isopropanol Drugs 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 1
- 102000034527 Retinoid X Receptors Human genes 0.000 description 1
- 108010038912 Retinoid X Receptors Proteins 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- YUHSMQQNPRLEEJ-UHFFFAOYSA-N methyl 3-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=CC(CBr)=C1 YUHSMQQNPRLEEJ-UHFFFAOYSA-N 0.000 description 1
- 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000000810 peripheral vasodilating agent Substances 0.000 description 1
- 229960002116 peripheral vasodilator Drugs 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- KRIOVPPHQSLHCZ-UHFFFAOYSA-N propiophenone Chemical compound CCC(=O)C1=CC=CC=C1 KRIOVPPHQSLHCZ-UHFFFAOYSA-N 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B63/00—Purification; Separation; Stabilisation; Use of additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/63—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
- C07C49/82—Ketones containing a keto group bound to a six-membered aromatic ring containing hydroxy groups
- C07C49/825—Ketones containing a keto group bound to a six-membered aromatic ring containing hydroxy groups all hydroxy groups bound to the ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
- C07D211/14—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hydrogenated Pyridines (AREA)
Abstract
A process for the preparation of 1-[4-(4-benzyloxy)phenyl]-2-(4-benzylpiperidin-1--yl)-1-propanone ("intermediate 3") comprises bromination of 4'-hydroxypropiophenone to give "intermediate 1", alkylation with 4-benzylpiperidine to give "intermediate 2", and benzylation with a benzyl halide (e.g. benzyl bromide) to give "intermediate 3". The latter may be purified by recrystallisation from hexane or heptane, or by forming a slurry in methanol at room temperature and causing solidification by cooling to 5{ C. In the preparation of intermediate 3, it is not necessary to isolate intermediates 1 and 2; organic solutions thereof may be used in the subsequent synthetic stage without evaporation of the solvent in vacuo. Reduction of intermediate 3 by temperature controlled lithium aluminium hydride reduction yields racemic erythro-ifenprodil and reduction of intermediate 3 by either sodium borohydride or catalytic hydrogen reduction yields racemic threo-ifenprodil.
Description
MANUFACTURE OF IFENPRODIL
Background of the Invention
Ifenprodil [a-(4-hydroxyphenyl)-13-methyl4(phenylmethyl>.iperidineethano1] is an a-adrenoreceptor antagonist and an NR2B selective NMDA antagonist used as a cerebral and peripheral vasodilator in the treatment of stroke. The drug substance is manufactured as the erythro-racemate by the route of Lab oratoire Robert et Carriere (US 3 509 164) utilising a key benzyl protected amino-ketone intermediate (3). In the established manufacturing process final hydrogenation provides the erythro relative stereochemistry of the drug substance (Scheme 1) The stage 2A bromination of intermediate la is characterized by high levels of impurities resulting from over bromination This intermediate is not suitable for use in Stage 3A without purification.
Scheme 1 HO STAGE IA PhO STAGE 2A 4-Hydroxyproplophenone Intermediate Ia C9H1002 [150 17] C16H1602 [150.17]
HN
r STAGE 3A Ph'O Intermediate 2a Intermediate 3 C16H1BrO2 [319 20] C28H31N02 [413.76] H2 I Pd - C STAGE4A HO-
IFENPRODIL
C21 H27NO [325 45] The Ifenprodil drug substance is isolated as one of two possible diastereoisomeric racemates. Racemic-erythro-ifenprodil is a combined NMDA and a-adrenoreceptor antagonist used as a vasodilator The corresponding threo- diastereoisomers are much more selective for NMIDA and as such represent promising opportunities for the treatment of pain and inflammatory conditions without the peripheral side effects expected from a- adrenoreceptor modulation.
Summary of the Invention
It has been found that, using a novel, truncated synthesis of intermediate 3, this can be used to provide either racemates of ifenprodil using only 2 isolation steps
Description of the Invention
In an improved process (Scheme 2), 4'-hydroxypropiophenone is brominated directly and the intermediate 4'-hydroxy-a-bromopropiophenone treated with 4- (phenylmethyl)piperidine in the presence of an organic base Intermediate 3 is then provided by benzylation under phase-transfer conditions Direct bromination of the 4'hydroxypropiophenone provides a cleaner brominated product (intermediate 1) facilitating its use in the alkylation step without isolation. Use of a pure intermediate 1 also leads to an intermediate 2 that is suitable for progression without isolation Thus, work up and purification provides intermediate 3 in up to 60% yield over the three stages without the need to isolate the stage 1 and stage 2 products Scheme 2 0 0 1HBr.Br2 CH2CI2 HO STAGEI HO Br 4-Hydroxypropiophenone Intermediate I C9H1002 [150.17] C9H9BrO2 [229 07] HN 0 PhBr Bu4NHSO4 NEt3/CH2CI2 CH2CI2 STAGE2 HO- STAGE3 Intermediate 2 C21HNO2 [323 43] (Y 1N) PhO Intermediate 3 C28H31N02 [413 76] Furthermore Intermediate 3 is provided in more than 97% purity allowing efficient control of this regulatory intermediate in the manufacture of racemic threo- ifenprodil (by temperature controlled lithium aluminium hydride reduction) or racemic erythro-ifenprodil (by sodium borohydride or catalytic hydrogen reduction).
In addition, Intermediate 3 is a useful precursor for the enantiospecific manufacture or (+)-threo-ifenprodil or (-)-threo-ifenprodil which are useful in the treatment of pain and inflammatory conditions. In summary this invention describes a much more efficient and cleaner manufacturing process for Intermediate 3 when compared to the route defined by Scheme 1.
Experimental: Stage 1: Bromination 4 Hvdroxv-a-bromopropiophenone (Intermediate 1) 4'-Hydroxypropiophenone (800g; 1.0 equiv.) was dissolved in dichloromethane (4. 8L; 6 vol.) and pyridinium tribromide (1 874g; 1.1 equiv.) added portionwise over 3 hours at room temperature. Complete reaction was confirmed by H NMR before the mixture was quenched with 10% w/v sodium thiosuiphate solution (1.6L; 2 vol.) over 10 minutes. The phases were separated and the lower dichloromethane layer containing intermediate I was retained for the alkylation reaction.
Stage 2: Alkylation 1 -[4-(phenylmethyl)-piperidine- l-yl]- 4' -hydroxypropiophenone (Intermediate 2) Triethylamine (1.48L; 2.0 equiv.) was added over 35 minutes to the stirred dichloromethane solution of Intermediate 1. A solution of 4-(phenylmethyl)piperidine (981mL; 1.05 equiv.) in dichioromethane (1.6L; 2 vol.) was then added over a period of 15 minutes at room temperature. The mixture was stirred overnight and complete reaction was confirmed by HPLC. The dichloromethane solution of intermediate 2 washed with water (I.6L; 2 vol) and retained for the benzylation reaction.
Stage 3 Benzylation 1 -[4-(phenylmethyl)-piperidine- l-yl]-4 -(benzyloxy)propiophenone (Intermediate 3) A solution of sodium hydroxide (l000g) in water (4.OL) was added over 30 minutes to the dichioromethane solution of intermediate 2. Tetrabutylammonium hydrogensulphate (271. 3g, 15 mol%) was added followed by the dropwise addition of benzylbromide (1.46L; 2.3 equiv.) at room temperature over a period of 28 hours.
Complete reaction was confirmed by HPLC before the layers were separated and the dichloromethane layer containing intermediate 3 washed sequentially with 10% w/v aqueous citric acid (2 x 1 6L, 2 vol.) and saturated sodium bicarbonate solution (2 x 1.6L; 2 vol).
The dichioromethane solution was concentrated in vacuo to produce a thick brown oil. Isopropylalcohol (2 4L; 3 vol.) was added and the mixture stirred overnight causing some crystallization The slurry is then cooled to 5 C over 2 hours and the crude intermediate 3 collected by filtration and washed with isopropylalcohol (0 8L; 1 vol.).
The crude, low melting solid is slurried in methanol (2.OL; 2.4 vol) at room temperature for 4 hours before cooling to 5 C for a further 1 hour. Intermediate 3 is isolated as a pale brown solid (1.1 - 1.3 Kg; 50- 60%) Melting Point: 87 - 89 C HPLC Purity: Typically >98%
Claims (12)
1-[4-(phenylmethyl)-piperidine-1- yl]-4'- (benzyloxy)propiophenone (Intermediate 3).
2. A process according to claim 1, where the starting material is 4'hydroxypropiophenone and 4'-hydroxy-a-bromopropiophenone (Intermediate 1) and 1 -[4-(phenylmethyl)-piperidine- l-yl] -4' -hydroxypropiophenone (Intermediate 2) are not isolated.
3 A process according to either preceding claim, where the stage 1 bromination is carried out with pyridinium tribromide
4 A process according to any preceding claim, where the solvent is dichioromethane.
A process according to any of claims 1 to 3, wherein the solvent is ethanol or isopropanol.
6. A process for robustly purifying 1-[4-(phenylmethyl)-piperidine-1-yl]4'- (benzyloxy)propiophenone (Intermediate 3).
7. A process according to claim 6, where the purification is recrystallisation from hexane or heptane.
8. A process according to claim 6, where the purification is by a sluny in methanol.
9. A process according to any preceding claim, where 1-[4-(phenylmethyl)piperidine-1-yl]-4'-(benzyloxy)propiophenone (Intermediate 3) is obtained with a purity of more than 98%.
10. A process according to any preceding claim, where the process is used in the manufacture of racemic-threo-ifenprodil.
11 A process according to any preceding claim, where the process is used in the manufacture of racemic-erythro-ifenprodil.
12. A process according to any preceding claim, where the process is used in the manufacture of (-)-threo-ifenprodil or (+)-threo-ifenprodil enantiomers.
13 A process according to any preceding claim, where the process is used in the manufacture of (-)-erythro-ifenprodil or (+)-erythro-ifenprodil enantiomers
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0519275A GB2430433A (en) | 2005-09-21 | 2005-09-21 | Preparation & purification of 1-[4-(4-benzyloxy)phenyl]-2-(4-benzylpiperidin-1-yl)-1-propanone, & use thereof in stereospecific preparation of ifenprodil |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0519275A GB2430433A (en) | 2005-09-21 | 2005-09-21 | Preparation & purification of 1-[4-(4-benzyloxy)phenyl]-2-(4-benzylpiperidin-1-yl)-1-propanone, & use thereof in stereospecific preparation of ifenprodil |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB0519275D0 GB0519275D0 (en) | 2005-11-02 |
| GB2430433A true GB2430433A (en) | 2007-03-28 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB0519275A Withdrawn GB2430433A (en) | 2005-09-21 | 2005-09-21 | Preparation & purification of 1-[4-(4-benzyloxy)phenyl]-2-(4-benzylpiperidin-1-yl)-1-propanone, & use thereof in stereospecific preparation of ifenprodil |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB2430433A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4690931A (en) * | 1982-10-13 | 1987-09-01 | Synthelabo | Therapeutically useful 1-phenyl-2-piperidinoalkanol derivatives |
-
2005
- 2005-09-21 GB GB0519275A patent/GB2430433A/en not_active Withdrawn
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4690931A (en) * | 1982-10-13 | 1987-09-01 | Synthelabo | Therapeutically useful 1-phenyl-2-piperidinoalkanol derivatives |
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| Publication number | Publication date |
|---|---|
| GB0519275D0 (en) | 2005-11-02 |
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| Date | Code | Title | Description |
|---|---|---|---|
| WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |