反应详情

温度

47.5 °C

(2R)-2-[[(4-Chlorophenyl)sulfonyl][(4-cyano-2-fluorophenyl)methyl]amino]-5,5,5-trifluoropentanamide (399 g) and methanol (1.6 L) were charged to a reactor followed by hydroxylamine (50% solution in water, 93 mL, 1.8 eq). The mixture was heated to 45-50° C. until complete reaction by HPLC (<0.15 relative AP starting material). Water (0.5 L) was charged slowly, keeping the batch temperature between 30-50° C. The batch was allowed to stand until crystallization started and then water (2.7 L) was charged. The batch was cooled to 15-20° C. and filtered. The cake was washed with 2:1 MeOH:water (2 L) and then dried under vacuum at 50° C. to give the title compound as white solid (415 g, 96% yield). 1H NMR (300 MHz, DMSO-d6) δ ppm 1.43-1.64 (m, 1 H) 1.77-1.93 (m, 1 H) 1.93-2.17 (m, 2 H) 4.41 (dd, J=8.48, 6.03 Hz, 1 H) 4.60 (d, J=17.14 Hz, 1 H) 4.94 (d, J=16.77 Hz, 1 H) 5.81-5.98 (m, 2 H) 7.19-7.27 (m, 1 H) 7.37-7.47 (m, 2 H) 7.52 (d, J=4.14 Hz, 2 H) 7.64 (d, J=8.67, Hz, 2 H) 7.85 (d, J=8.85 Hz, 2 H) 9.71-9.83 (m, 1 H). IR (KBr): 3491, 3379, 1680, 1651, 1592, 1433, 1343. Anal. Calcd. for Cr19H19ClF4N4O4S Calc. C, 44.66; H, 3.74; N, 10.96; S, 6.27; F, 14.87; Cl, 6.94. Found: C, 44.90; H, 3.91; N, 10.91; S, 6.41; F, 15.21; Cl, 6.95.

1. custombetween 30-50° C
2. customto stand until crystallization
3. additionwater (2.7 L) was charged
4. temperatureThe batch was cooled to 15-20° C.
5. filtrationfiltered
6. washThe cake was washed with 2:1 MeOH
7. dry with materialwater (2 L) and then dried under vacuum at 50° C.