Diisopropyl Ether → HCID 12099060, compound

Following the general procedure, 4,5,6,7-tetrahydrobenzofuran-7-ylamine (150 mg, 1.09 mmol), CALB (45 mg), EtOAc (0.43 mL) and iPr2O (4.0 mL) were stirred for 17 hours. The conversion determined from 1H NMR by integration of the peaks at 5.09 ppm (CHNHAc) and 3.95 ppm (CHNH2) was 55%. Flash chromatography of the material on silica gel using 1:20 MeOH:CH2Cl2 followed by 1:1:4 NH4OH:MeOH:CH2Cl2 furnished (R)—N-(4,5,6,7-tetrahydrobenzofuran-7-yl)acetamide ((104 mg, 53%) in 79% ee (chiral GC method: 120° C. for 15 min, ramp rate of 2° C./min to 160° C., hold 20 min at 160° C., (S)-(−)-enantiomerrt43.6 min (R)-(+)-enantiomerrt=45.8 min); [α]D=+58° (c 1.04, CHCl3); 1H NMR (CDCl3, 300 MHz) δ 1.65–1.86 (m, 3H), 1.90–1.2.04 (m, 1H), 1.94 (s, 3H), 2.30–2.50 (m, 2H), 5.09 (br s, 1H), 6.16 (s, 1H), 7.24 (s, 1H); 13C NMR (CDCl3) δ 20.6, 22.4, 23.6, 31.0, 43.6, 110.7, 120.9, 142.2, 148.8, 170.1; MS m/z: 180 (M+H+). The unreacted (S)-4,5,6,7-tetrahydrobenzofuran-7-ylamine (was isolated in 39% yield (59 mg) and 94% ee (chiral GC, (S)-enantiomerrt=12.6 min, (R)-enantiomerrt=13.5 min); [α]D=−18° (c 0.59, CHCl3); 1H NMR (CDCl3, 300 MHz): δ 1.50–1.75 (m, 4H), 1.76–1.90 (m, 1H), 2.01–2.20 (m, 1H), 2.30–2.50 (m, 2H), 3.94 (t, 1H, J=5.7 Hz), 6.17 (d, 1H, J=1.5 Hz), 7.26 (d, 1H, J=1.5 Hz); 13C NMR (CDCl3): δ 21.1, 22.6, 34.0, 45.5, 110.5, 117.9, 141.3, 153.6; MS m/z: 160 (M+Na+).

ORD record

ord-9c3992ce42284d57909f9c4ed7cd425b

Source dataset

uspto-grants-2006_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07135570B2