反应详情

A solution of (S)-1-[3-ethyl-5-(1-methyl-1H-tetrazol-5-yl)-phenyl]-3-{1-[2-(4-fluorophenyl)-2-oxo-ethyl]-piperidin-3-ylmethyl}-urea (23 mg, 48 μmol) in methanol (1.0 mL) was treated with sodium borohydride (4.5 mg, 120 μmol) and the mixture was stirred at room temperature. After 3 hours and again after 5 hours, additional sodium borohydride (ca. 2 mg) was added. After a total of 7 hours, water (0.5 mL) was added, and the mixture was concentrated under vacuum. The residue was purified by flash column chromatography, eluting with 3% methanol in dichloromethane containing 0.3% aqueous ammonia, to provide a white glassy solid (21 mg, 91%). This material was a 1:1 mixture of epimers at the hydroxyl group. 1H NMR (300 MHz, CDCl3) δ8.25+8.16 (2s, 1H), 7.75+7.70 (2s, 1H), 7.54 (s, 1H), 7.30 (m, 2H), 7.05 (s, 1H), 7.00 (t, J=9 Hz, 2H), 6.21+6.13 (2 bt, 1H), 4.71 (m, 1H), 4.15+4.14 (2 s, 3H), 3.3-3.1 (m, 3H), 3.0-2.7 (m, 3H), 2.60 (q, J=8 Hz, 2H), 2.5-2.3 (m, 3H), 2.3-2.1 (2m, 1H), 1.9-1.5 (m, 4H), 1.20+1.19 (2 t, J=8 Hz, 3H) Mass spec (ES+) m/z 482.4 (M+H+).

1. waitagain after 5 hours
2. concentrationthe mixture was concentrated under vacuum
3. customThe residue was purified by flash column chromatography
4. washeluting with 3% methanol in dichloromethane containing 0.3% aqueous ammonia