反应详情

To a solution of (N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine (Preparation 14, 40.6 g, 0.1619 mol) in anhydrous tetrahydrofuran (600. mL), cooled to −70° C., under nitrogen was added lithium 1,1,1,3,3,3-hexamethyldisilazan-2-ide (1 M in tetrahydrofuran, 161.9 mL, 0.161.9 mol) drop wise. The reaction mixture was warmed to room temperature and stirred for 1 hour before cooling to −70° C. A solution of 5-chloro-2,4-difluorobenzenesulfonyl chloride (40 g, 0.1619 mol) in tetrahydrofuran (200.0 mL) was added dropwise. After complete addition, the reaction mixture was gradually warmed to room temperature and stirred for 1 hour. Reaction mixture was quenched with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. Organic layer was washed with water and saturated aqueous sodium chloride solution. Crude residue was purified by column chromatography eluting with ethyl acetate:hexane (gradient 1:19 to 3:17, by volume) to afford the title compound as a white solid, 46 g.

1. temperaturebefore cooling to −70° C
2. additionAfter complete addition
3. temperaturethe reaction mixture was gradually warmed to room temperature
4. stirringstirred for 1 hour
5. customReaction mixture
6. customwas quenched with saturated aqueous ammonium chloride solution
7. extractionextracted with ethyl acetate
8. washOrganic layer was washed with water and saturated aqueous sodium chloride solution
9. customCrude residue was purified by column chromatography
10. washeluting with ethyl acetate