反应详情

Following the general procedure, 2-methyl-5,6,7,8-tetrahydroquinolin-8-ylamine (412.7 mg, 2.78 mmol), CALB (128 mg), EtOAc (0.63 mL) and iPr2O (7 mL) were stirred for 9 hours. The conversion determined from 1H NMR by integration of the peaks at 4.73 ppm (CHNHAc) and 4.00 ppm (CHNH2) was 51%. Flash chromatography of the material on silica gel using 1:10 MeOH:CH2Cl2 then 10:1:1 CH2Cl2—MeOH—NH4OH furnished (R)-N-(2-methyl-5,6,7,8-tetrahydroquinolin-8-yl)acetamide ((167 mg, 47%) in 88% ee (chiral GC method: initial temperature 140° C., initial time 22 minutes, ramp rate 1° C./min, final temperature 150° C., final time 70 min, (S)-enantiomerrt=89.4 min, (R)-enantiomer =91.6 min); [α]D=−102° (c 1.67, CHCl3); 1H NMR (CDCl3, 300 MHz) δ 1.56-1.66 (m, 1H), 1.82-1.91 (m, 2H), 2.08 (s, 3H), 2.51 (s, 3H), 2.61 (ddd, 1H, J=13.2, 5.1, 5.1 Hz), 2.76 (t, 1H, J=6.6 Hz), 4.72-4.79 (m, 1H), 6.61 (br s, 1H), 6,98 (d, 1H, J=7.8 Hz), 7.31 (d, 1H, J=7.8 Hz); 13C NMR (CDCl3) δ 20.1, 23.8, 24.2, 28.2, 29.6, 51.5, 122.4, 130.1, 137.8, 154.4, 155.7, 170.8; MS m/z: 205 (M+H+), 146 (M-NHAc). The unreacted (S)-2-methyl-5,6,7,8-tetrahydroquinolin-8-ylamine (was isolated in 38% yield (107 mg) and 91% ee (chiral GC: (S)-enantiomerrt=19.9 min, (R)-enantiomerrt=20.6 min); [α]D=+65° (c 1.07, CHCl3); 1H NMR (CDCl3, 300 MHz) δ 1.62-1.82 (m, 2H), 1.84-2.00 (m, 3H), 2.11-2.20 (m, 1H), 2.49 (s, 3H), 2.61-2.82 (m, 2H), 3.93-4.00 (m, 1H), 6.91 (d, 1H, J=7.8 Hz), 7.25 (d, 1H, J=7.8 Hz); 13C NMR (CDCl3) δ 20.4, 24.6, 29.1, 32.6, 51.8, 121.7, 128.6, 137.6, 155.9, 159.0; MS m/z: 163 (M+H+).