反应详情

温度

57.5 °C

N-((4aS,5S,7aS)-7a-(2,3-difluorophenyl)-5-(fluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide (19.40 g, 0.048 mol, 1.0 equiv.) was dissolved in methanol (97 mL), under nitrogen. 1,8-diazabicyclo[5.4.0]undec-7-ene (8.92 mL, 0.060 mol, 1.25 equiv.) was added, and the solution was heated to 55-60° C. After 8 h, the reaction mixture was concentrated under reduced pressure, and the residue purified by silica gel flash column chromatography (5% to 100% EtOAc in heptane) to afford the title compound (9.01 g). 1H NMR (500 MHz, DMSO) δ ppm 7.38-7.28 (m, 1H), 7.26-7.14 (m, 2H), 6.12 (s, 2H), 4.66-4.41 (m, 2H), 4.37-4.27 (m, 2H), 4.29 (d, J=8.2 Hz, 1H), 3.74 (dd, J=8.2, 2.6 Hz, 1H), 3.30 (s, 1H), 3.06-2.90 (m, 2H), 2.79-2.71 (m, 1H); 13C NMR (125 MHz, DMSO) δ ppm 150.84 (dd, J=244.8, 14.0 Hz), 149.71, 148.07 (dd, JCF=247.8, 13.4 Hz), 133.08 (d, JCF=7.7 Hz), 125.24, 124.55 (dd, JCF=7.2, 4.3 Hz), 116.58 (d, JCF=17.2 Hz), 83.91 (d, JCF=170.0 Hz), 79.12 (d, JCF 18.2 Hz), 77.96 (d, JCF=4.9 Hz), 66.22, 36.41 (d, JCF=3.3 Hz), 23.40.

1. concentrationthe reaction mixture was concentrated under reduced pressure
2. customthe residue purified by silica gel flash column chromatography (5% to 100% EtOAc in heptane)