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 (10 g, 21.7 mmol, Eq: 1.00) and ethyl thioglycolate (3.92 g, 3.57 ml, 32.6 mmol, Eq: 1.5) in DMF (134 ml) was added at 23° C. 1,1,3,3-tetramethylguanidine (3.75 g, 4.09 ml, 32.6 mmol, Eq: 1.5). The reaction mixture was stirred at 23° C. for 16 hours. The solution was evaporated at HV. The resulting residue was stirred vigorously overnight between 100 ml of dichloromethane and 20% (v/v) sulfuric acid solution (100 ml). Sat. NaHCO3-solution was slowly added (pH=8), then extracted with dichloromethane twice. The combined organic layers were dried over Na2SO4, filtered and evaporated to give the crude product (14.4 g, 132%). The residue was chromatographed on 70 g silica gel with 0-50% ethyl acetate in heptane to give the (R)-ethyl 2-(2-(5-bromo-2-fluorophenyl)-2-(2,4-dimethoxybenzylamino)propylthio)acetate (10.9 g, 21.8 mmol, 100% yield) as a light yellow oil. MS (ISP): m/z=500.2 [M+H]+ and 502.2 [M+2+H]+.

1. customThe solution was evaporated at HV
2. stirringThe resulting residue was stirred vigorously overnight between 100 ml of dichloromethane and 20% (v/v) sulfuric acid solution (100 ml)
3. additionSat. NaHCO3-solution was slowly added (pH=8)
4. extractionextracted with dichloromethane twice
5. dry with materialThe combined organic layers were dried over Na2SO4
6. filtrationfiltered
7. customevaporated
8. customto give the crude product (14.4 g, 132%)
9. customThe residue was chromatographed on 70 g silica gel with 0-50% ethyl acetate in heptane