【结 构 式】 |
【药物名称】Phenylephrine hydrochloride, SLV-325, Incostop, Neo-Synephrine hydrochloride, Nostril, Mydfrin, Biomydrin, Alcon Efrin 【化学名称】(-)-3-[1(R)-Hydroxy-2-(methylamino)ethyl]phenol hydrochloride 【CA登记号】61-76-7, 59-42-7 (free base) 【 分 子 式 】C9H14ClNO2 【 分 子 量 】203.67043 |
【开发单位】Solvay (Marketer), SLA Pharma (Licensee) 【药理作用】Anorectal Disorders, Treatment of, GASTROINTESTINAL DRUGS |
合成路线1
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.
【1】 Gurjar, M.K.; et al.; A practical synthesis of (R)-(-)-phenylephrine hydrochloride. Org Process Res Dev 1998, 2, 6, 422. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
11021 | Methanamine; Methylamine | 74-89-5 | CH5N | 详情 | 详情 | |
40670 | 2-(chloromethoxy)ethyl methyl ether; 1-(chloromethoxy)-2-methoxyethane; (2-methoxyethoxy)methyl chloride | 3970-21-6 | C4H9ClO2 | 详情 | 详情 | |
(I) | 28537 | 3-hydroxybenzaldehyde | 100-83-4 | C7H6O2 | 详情 | 详情 |
(II) | 36802 | 3-[(2-methoxyethoxy)methoxy]benzaldehyde | C11H14O4 | 详情 | 详情 | |
(III) | 29693 | Trimethylsulfoxonium iodide | 1774-47-6 | C3H9IOS | 详情 | 详情 |
(IV) | 36803 | (2-methoxyethoxy)methyl 3-(2-oxiranyl)phenyl ether; 2-[3-[(2-methoxyethoxy)methoxy]phenyl]oxirane | C12H16O4 | 详情 | 详情 | |
(V) | 36804 | (1S)-1-[3-[(2-methoxyethoxy)methoxy]phenyl]-1,2-ethanediol | C12H18O5 | 详情 | 详情 | |
(VI) | 36805 | (2-methoxyethoxy)methyl 3-[(2R)oxiranyl]phenyl ether; (2R)-2-[3-[(2-methoxyethoxy)methoxy]phenyl]oxirane | C12H16O4 | 详情 | 详情 | |
(VII) | 36806 | (1R)-1-[3-[(2-methoxyethoxy)methoxy]phenyl]-2-(methylamino)-1-ethanol | C13H21NO4 | 详情 | 详情 |