反应详情

温度

23 °C

To a solution of (R)-4-(5-Bromo-2-fluoro-phenyl)-3-(2,4-dimethoxy-benzyl)-4-methyl-[1,2,3]oxathiazolidine 2,2-dioxide (5.1 g, 11.1 mmol, Eq: 1.00) and 1,1,3,3-tetramethylguanidine (1.91 g, 2.09 ml, 16.6 mmol, Eq: 1.5) in DMF (77.3 ml) was added at 23° C. 2-mercaptoacetonitrile (1.22 g, 16.6 mmol, Eq: 1.5) dropwise. The reaction mixture was stirred at 23° C. for 16 hours. All volatiles were was evaporated at high vacuum and the resulting residue was stirred vigorously between 60 ml of dichloromethane and 20% (v/v) sulfuric acid solution (60 ml) for 40 hours. Sat. NaHCO3 solution was slowly added (pH=8), then extracted twice with dichloromethane. The combined organic layers were dried over Na2SO4, filtered and evaporated. The residue was purified by silica gel column chromatography with 0-50% ethyl acetate in heptane to give (R)-2-(2-(5-bromo-2-fluorophenyl)-2-(2,4-dimethoxybenzylamino)propylthio)acetonitrile (5.2 g, 10.9 mmol, 98.3% yield) as a light brown oil. MS (ISP): m/z=453.0 [M+H]+ and 455.2 [M+2+H]+.

1. customAll volatiles were was evaporated at high vacuum
2. stirringthe resulting residue was stirred vigorously between 60 ml of dichloromethane and 20% (v/v) sulfuric acid solution (60 ml) for 40 hours
3. additionSat. NaHCO3 solution was slowly added (pH=8)
4. extractionextracted twice with dichloromethane
5. dry with materialThe combined organic layers were dried over Na2SO4
6. filtrationfiltered
7. customevaporated
8. customThe residue was purified by silica gel column chromatography with 0-50% ethyl acetate in heptane