反应详情

Thionyl chloride (3.9 ml, 5.3 mmol) was added dropwise to a solution of (2R)-3-bromo-2-hydroxy-2-methylpropionic acid (8.19 g, 44.8 mmol, prepared as described in WO 2005/000794) in 190 ml of THF and 5.8 ml of N,N-dimethyl-acetamide (DMAC) at 5° C. under nitrogen atmosphere. The solution was stirred for 3 h at room temperature. A solution of 5-amino-2-cyanobenzoic acid methyl ester (7.50 g, 4.3 mmol) in 75 ml of THF was added and the reaction mixture was maintained at 50° C. for 3 h and at room temperature for 16 h. The mixture was poured into water, extracted with ethyl acetate, washed with water, dried over Na2SO4 and evaporated under reduced pressure. The crude product was stirred in toluene and filtration afforded the purified compound.

1. temperaturethe reaction mixture was maintained at 50° C. for 3 h and at room temperature for 16 h
2. extractionextracted with ethyl acetate
3. washwashed with water
4. dry with materialdried over Na2SO4
5. customevaporated under reduced pressure
6. stirringThe crude product was stirred in toluene
7. filtrationfiltration
8. customafforded the purified compound