- 【药物名称】Phenylephrine hydrochloride, SLV-325, Incostop, Neo-Synephrine hydrochloride, Nostril, Mydfrin, Biomydrin, Alcon Efrin
- 【化学名】(-)-3-[1(R)-Hydroxy-2-(methylamino)ethyl]phenol hydrochloride
- 【CAS登记号】61-76-7, 59-42-7 (free base)
- 【结构式】
- 【分子式】C9-H13-N-O2.Cl-H
- 【分子量】203.6676
- 【原研厂家】Solvay (Marketer), SLA Pharma (Licensee)
- 【作用类别】Anorectal Disorders, Treatment of, GASTROINTESTINAL DRUGS
- 【研发状态】Launched
- 【合成情况】
- 〖来源〗Org Process Res Dev
- 〖合成路线〗
- 〖标题〗A practical synthesis of (R)-(-)-phenylephrine hydrochloride
- 〖合成方法〗3-Hydroxybenzaldehyde (I) was protected as the methoxyethoxymethyl ether derivative (II) by treatment with methoxyethoxymethyl chloride and diisopropyl ethyl amine. Subsequent condensation of (II) with dimethyloxosulfonium methylide, generated from oxosulfonium salt (III) and NaH, gave rise to the racemic epoxide (IV). Kinetic resolution by hydrolysis with (R,R)-N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediaminocobalt (III) acetate complex provided the (S)-diol (V) along with the unreacted (R)-epoxide (VI), which were separated by column chromatography. Opening of the desired (R)-epoxide (VI) with methanolic methylamine gave amino alcohol (VII). Finally, removal of the methoxyethoxymethyl group by refluxing in methanolic HCl furnished the title compound.
- 〖作者〗Gurjar, M.K.; et al.
- 〖参考〗Gurjar, M.K.; et al.; A practical synthesis of (R)-(-)-phenylephrine hydrochloride. Org Process Res Dev 1998, 2, 6, 422
- 〖出处〗Org Process Res Dev1998,2,(6):422
- 〖备注〗Synthesis of 070250: 3-Hydroxybenzaldehyde (I) was protected as the methoxyethoxymethyl ether derivative (II) by treatment with methoxyethoxymethyl chloride and diisopropyl ethyl amine. Subsequent condensation of (II) with dimethyloxosulfonium methylide, generated from oxosulfonium salt (III) and NaH, gave rise to the racemic epoxide (IV). Kinetic resolution by hydrolysis with (R,R)-N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediaminocobalt (III) acetate complex provided the (S)-diol (V) along with the unreacted (R)-epoxide (VI), which were separated by column chromatography. Opening of the desired (R)-epoxide (VI) with methanolic methylamine gave amino alcohol (VII). Finally, removal of the methoxyethoxymethyl group by refluxing in methanolic HCl furnished the title compound. (Scheme 07025001a)
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