【结 构 式】 |
【分子编号】36805 【品名】(2-methoxyethoxy)methyl 3-[(2R)oxiranyl]phenyl ether; (2R)-2-[3-[(2-methoxyethoxy)methoxy]phenyl]oxirane 【CA登记号】 |
【 分 子 式 】C12H16O4 【 分 子 量 】224.25664 【元素组成】C 64.27% H 7.19% O 28.54% |
合成路线1
该中间体在本合成路线中的序号:(VI)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 |