反应详情

温度

-10 °C

To a solution of 2,2-bis-difluoromethyl-2-hydroxyacetic acid (0.5 g, 2.84 mmoles) in dimethyl acetamide (10 ml) at -10° C. was added thionyl chloride (0.34 g, 2.84 mmole)s) dropwise. The resulting solution was stirred at -10° C. for approximately 30 mins. 4-(2-pyrimidylsulfonyl)aniline (0.59 g, 2.5 mmoles) was added and the reaction mixture was stirred overnight at room temperature. The reaction mixture was poured into water, and sodium bicarbonate solution was added to give a pH of 7-7.5. A dark colored precipitate was formed that was filtered, washed with water and dried. The crude material was preabsorbed onto silica gel and chromatographed on silica gel eluting with 70-80% ethyl/acetate/hexane. Evaporation of product-containing fractions and crystallization from methylene chloride/methanol/hexane gave the title compound (0.33 g, 34%) as a white solid; mp 209°-210° C. 1H--NMR (300 MHz, d6 --DMSO):6.46(t, J=54.06 Hz, 2H, HCF 2), 7.78 (t, J=4.8 Hz, 1H, ArH), 7.95-7.98(m, 3H, ArH, OH), 8.02-8.06(m, 2H, ArH), 9.01 (d, J=5.01 Hz, 2H, ArH), 10.58 (s, 1H, NH). MS(CI):394(M+1, 100%).

1. stirringthe reaction mixture was stirred overnight at room temperature
2. additionwas added
3. customto give a pH of 7-7.5
4. customA dark colored precipitate was formed
5. filtrationthat was filtered
6. washwashed with water
7. customdried
8. customThe crude material was preabsorbed onto silica gel
9. customchromatographed on silica gel eluting with 70-80% ethyl/acetate/hexane
10. customEvaporation of product-containing fractions and crystallization from methylene chloride/methanol/hexane