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)δ 1.09–1.31 (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-dfb74fca910f43e6815637d27a0a7606

Source dataset

uspto-grants-2006_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07135570B2