Ethyl Acetate → N-[(4R)-3,4-Dihydro-2H-pyrano[3,2-b]pyridin-4-yl]acetamide

Following the general procedure, 3,4-dihydro-2H-pyrano[3,2-b]pyridin-4-ylamine (243 mg, 1.62 mmol), CALB (73 mg) and EtOAc (6.0 mL) were stirred for 2 hours. The conversion determined from 1H NMR by integration of the peaks at 7.93 ppm and 8.16 ppm was 50% (CHNH2 and CHNHAc signals were not distinct). Flash chromatography of the material on silica gel using 1:10 MeOH:CH2Cl2 followed by 1:1:10 NH4OH:MeOH:CH2Cl2 furnished the (R)-N-(3,4-dihydro-2H-pyrano[3,2-b]pyridin-4-yl)acetamide ((145 mg, 47%) in 98% ee (chiral GC method: 140° C. for 16 min, ramp rate 5° C./min to 160° C., hold at 160° C. for 50 min, (S)-enantiomerrt=41.5 min, (R)-enantiomerrt=40.9 min); [α]D=−69° (c 1.45, CHCl3); 1H NMR (CDCl3, 300 MHz) δ 1.91-2.00 (m, 1H), 1.97 (s, 3H), 2.47-2.57 (m, 1H), 4.18-4.22 (m, 2H), 4.85-4.92 (m, 1H), 6.97 (m, 2H), 7.24 (br s, 1H), 7.93-7.95 (dd, 1H, J=1.8, 3.9 Hz); 13C NMR (CDCl3) δ 23.3, 28.9, 47.2, 64.4, 124.3, 124.7, 141.3, 141.7, 152.0, 170.9; MS m/z: 215 (M+Na+). The unreacted (S)-3,4-dihydro-2H-pyrano[3,2-b]pyridin-4-ylamine (was isolated in 43% yield (104 mg) and 99% ee ((S)-enantiomerrt=14.7 min, (R)-enantiomerrt=15.6 min); [α]D=−13° (c 0.72, CHCl3); 1H NMR (CDCl3, 300 MHz): δ 1.84 (br s, 2H), 1.90-2.01 (m, 1H), 2.24-2.34 (m, 1H), 4.12 (dd, 1H, J=5.7, 6.9 Hz), 4.18-4.26 (m, 1H), 4.28-4.36 (m, 1H), 7.06-7.13 (m, 2H), 8.15 (dd, 1H, J=1.8, 3.6 Hz); 13C NMR (CDCl3) δ 31.5, 47.8, 64.2, 123.8, 124.5, 142.1, 147.0, 151.1; MS m/z: 151.0 (M+H+), 134.0 (M−NH2); Anal. Calc. for C8H10N2O. 0.1H2O: C, 63.22; H, 6.76; N, 18.43. Found: C, 62.99; H, 6.81; N, 18.22.

ORD record

ord-9bae3b7ce0be4650936ca3ab74c2dbf9

Source dataset

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07452994B2