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【结 构 式】 
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【分子编号】57176 【品名】(2S)-2-hydroxy-2-phenylethyl 4-methylbenzenesulfonate 【CA登记号】 |
【 分 子 式 】C15H16O4S 【 分 子 量 】292.35564 【元素组成】C 61.63% H 5.52% O 21.89% S 10.97% |
合成路线1
该中间体在本合成路线中的序号：(III)The asymmetric dihydroxylation of styrene (I) by means of K3Fe(CN)6 and OsO4, catalyzed by 1,4-bis(dihydroquinin-9-O-yl)phthalazine ((DHQ)2PHAL)in tert-butanol/water gives the 1(R)-phenylethane-1,2-diol (II), which is treated with Ts-Cl and pyridine in dichloromethane to yield the monotosylate (III). The reaction of (III) with NaCN in Et-OH/water affords 3(R)-hydroxy-3-phenylpropionitrile (IV), which is reduced by means of BH3/Me2S in refluxing THF to provide the corresponding amine (V). The O-alkylation of (V) with 4-(trifluoromethyl)chlorobenzene (VI) by means of NaH in hot DMSO gives 3(R)-phenyl-3-[4(trifluoromethyl)phenoxy]propylamine (VII), which is treated with methyl chloroformate (VIII) and K2CO3 in dichloromethane to yield the carbamate (IX) Finally, this compound is reduced by means of LiAlH4 in THF to provide the target (R)-fluoxetine.
| 【1】 Pandey, R.K.; et al.; An asymmetric dihydroxylation route to enantiomerically pure norfluoxetine and fluoxetine. Tetrahedron Lett 2002, 43, 25, 4425. |
| 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) | 19649 | 1-vinylbenzene | 100-42-5 | C8H8 | 详情 | 详情 |
| (II) | 57175 | R(-)-1-Phenyl-1,2-ethanediol R(-)-Phenylethylene glycol | C8H10O2 | 详情 | 详情 | |
| (III) | 57176 | (2S)-2-hydroxy-2-phenylethyl 4-methylbenzenesulfonate | C15H16O4S | 详情 | 详情 | |
| (IV) | 57177 | (3R)-3-hydroxy-3-phenylpropanenitrile | C9H9NO | 详情 | 详情 | |
| (V) | 57178 | (1R)-3-amino-1-phenyl-1-propanol | C9H13NO | 详情 | 详情 | |
| (VI) | 11973 | 1-Chloro-4-(trifluoromethyl)benzene; 4-Chlorobenzotrifluoride | 98-56-6 | C7H4ClF3 | 详情 | 详情 |
| (VII) | 57179 | (3R)-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propylamine; (3R)-3-phenyl-3-[4-(trifluoromethyl)phenoxy]-1-propanamine | C16H16F3NO | 详情 | 详情 | |
| (VIII) | 16993 | methyl chlorocarbonate;Carbonochloridic acid methyl ester；[(chlorocarbonyl)oxy]methane；methyl chloroformate | 79-22-1 | C2H3ClO2 | 详情 | 详情 |
| (IX) | 57180 | methyl (3R)-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propylcarbamate | C18H18F3NO3 | 详情 | 详情 |