|
【结 构 式】 
|
【分子编号】44328 【品名】(1R)-3-chloro-1-phenylpropyl 2-methylphenyl ether; 1-[[(1R)-3-chloro-1-phenylpropyl]oxy]-2-methylbenzene 【CA登记号】114446-47-8 |
【 分 子 式 】C16H17ClO 【 分 子 量 】260.76308 【元素组成】C 73.7% H 6.57% Cl 13.6% O 6.14% |
合成路线1
该中间体在本合成路线中的序号：(VI)A new synthesis of tomoxetine has been described: The reduction of omega-chloropropiophenone (I) with NaBH4 in ethanol gives 3-chloro-1-phenyl-1-propanol (II), which is treated with butyric anhydride and pyridine in dichloromethane to yield the corresponding racemic ester (III). The optical resolution of (III) with immobilized lipase B from Candida antarctica (CALB) affords a mixture of unreacted (S)-ester and (R)-alcohol (IV) that are separated by column chromatography. Condensation of th (R)-alcohol (IV) with 2-methylphenol (V) by means of PPh3 and diethyl azodicarboxylate (DEAD) in THF gives the corresponding ether (VI), which is finally treated with methylamine in refluxing ethanol.
| 【1】 Anthonsen, T.; Ho, B.H.; Liu, H.L.; Chemoenzymatic synthesis of the non-tricyclic antidepressants fluoxetine, tomoxetine and nisoxetine. J Chem Soc - Perkins Trans I 2000, 11, 11, 1767. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 28073 | 3-chloro-1-phenyl-1-propanone | 936-59-4 | C9H9ClO | 详情 | 详情 |
| (II) | 28074 | 3-chloro-1-phenyl-1-propanol | C9H11ClO | 详情 | 详情 | |
| (III) | 37781 | 3-chloro-1-phenylpropyl butyrate | C13H17ClO2 | 详情 | 详情 | |
| (IV) | 37782 | (1R)-3-chloro-1-phenyl-1-propanol | C9H11ClO | 详情 | 详情 | |
| (V) | 10010 | o-Cresol | 95-48-7 | C7H8O | 详情 | 详情 |
| (VI) | 44328 | (1R)-3-chloro-1-phenylpropyl 2-methylphenyl ether; 1-[[(1R)-3-chloro-1-phenylpropyl]oxy]-2-methylbenzene | 114446-47-8 | C16H17ClO | 详情 | 详情 |