Diisopropyl Ether → N-[(9R)-6,7,8,9-Tetrahydro-5H-cyclohepta[b]pyridin-9-yl]acetamide

Following the general procedure, 6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ylamine (195 mg, 1.20 mmol), CALB (59 mg), EtOAc (0.48 mL) and iPr2O (4.6 mL) were stirred for 24 hours. The conversion determined from 1H NMR by integration of the peaks at 5.05 ppm (CHNHAc) and 4.34 ppm (CHNH2) was 58%. Flash chromatography of the material on silica gel using 1:10 MeOH:CH2Cl2 followed by 1:1:4 NH4OH:MeOH:CH2Cl2 furnished the (R)-N-(6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-yl)acetamide ((134 mg, 55%) in 45% ee (chiral GC method: 180° C. for 15 min, ramp rate of 10° C./min to 210° C., hold 10 min, (S)-(−)-enantiomerrt=17.4 min, (R)-(+)-enantiomerrt=17.1 min); [α]D=−10° (c 1.34, CHCl3); 1H NMR (CDCl3, 300 MHz) 61.09-1.31 (m, 2H), 1.80-2.03 (m, 3H), 2.06 (s, 3H), 2.24 (d, 1H, J=13.5 Hz), 2.65-2.71 (m, 1H), 2.75-2.85 (m, 1H), 4.96-5.01 (m, 1H), 7.06 (dd, 1H, J=7.0, 4.8 Hz), 7.38 (d, 1H, J=7.0 Hz), 8.11 (br s, 1H), 8.28 (d, 1H, J=4.8 Hz); 13C NMR (CDCl3) δ 24.0, 27.3, 30.1, 34.5, 34.8, 53.8, 122.8, 137.0, 137.5, 145.5, 159.2, 169.6; MS m/z: 205 (M+H+). The unreacted (S)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-ylamine (was isolated in 41% yield (81 mg) and 61% ee (chiral GC, (S)-enantiomerrt=5.81 min, (R)-enantiomerrt=6.00 min); [α]D=+2° (c 1.13, CHCl3); and displayed spectra identical to the starting material: 1H NMR (CDCl3, 300 MHz) δ 1.20-1.35 (m, 1H), 1.36-1.53 (m, 1H), 1.75-2.01 (m, 4H), 2.15 (br s, 2H), 2.69-2.77 (m, 2H), 4.16 (d, 1H, J=8.7 Hz), 6.95-7.06 (m, 1H), 7.32 (d, 1H, J=6.0 Hz), 8.34 (br s, 1H).

ORD record

ord-63bc78a098784da6afe16ce3ab6d9089

Source dataset

uspto-grants-2004_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06825351B2