(1S)-2-chloro-1-(3,4-difluorophenyl)-1-ethanol synthesis

Yield:1006376-60-8 98.9%

Reaction Conditions:

with borane-THF;(S)-1-methyl-3,3-diphenyl-hexahydropyrrolo[1,2-c][1,3,2]oxazaborole in toluene at 10; for 3 h;Inert atmosphere;Corey-Bakshi-Shibata Reduction;Reagent/catalyst;Temperature;

Steps:

35 Preparation of 2-chloro-1S-(3,4-difluorophenyl)ethanol (Compound V)
Under nitrogen, to a dry 1L four-necked flask, was added (S) -CH₃-CBS (1mol / L toluene solution, 15.6ml, 0.01mol), it was added BH ₃· THF (1mol / L toluene solution, 110.2ml, 0.11mol), stirred for 1h at 10 . Toluene was slowly added dropwise compound (30g, 0.16mol) in (160 ml) solution, dropwise for about 2h. The reaction 1h at 10 . Temperature below 10 , to the reaction was added dropwise dilute sulfuric acid (0.2mol / L, 200ml). The addition was completed, stirring at 25 deg.] C 30min. It was allowed to separate, and the organic layer was saturated sodium bicarbonate solution (400ml), washed with water (400ml). Dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to give a yellow oil compound (29.9g, 98.9%), HPLC purity 96.5%, ee value 98.9%

References:

Shanghai Pharmaceutical Industry Institute;China Pharmaceutical Industry Zongyuan;Zhang Fuli;Xu Jianguo;He Xiaoqing;Wu Taizhi;Gu Honglei CN104974017, 2017, B Location in patent:Paragraph 0103-0106