Isopropanol → HCID 71278253, compound

Participants

Reaction Steps

The sodium salt of 2-propanol (34 mg, 0.41 mmol) was dissolved in 2-propanol (1.5 mL), and this was added to a solution of [(4aR,6R,8aS)-2-[(tert-butoxycarbonyl)amino]-8a-(2-fluorophenyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-6-yl]methyl methanesulfonate (C19) (40 mg, 0.084 mmol) in 2-propanol (0.5 mL). After 18 hours, additional sodium salt (34 mg, 0.41 mmol) was added, and stirring was continued for 66 hours. After addition of aqueous ammonium chloride solution, the mixture was extracted three times with ethyl acetate. The combined organic layers were washed with water, washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated in vacuo. Purification was carried out via preparative thin layer chromatography on silica gel (Eluent: 1:1 ethyl acetate/heptane) to provide the product as a white foam. Yield: 11.2 mg, 0.255 mmol, 30%. LCMS m/z 439.4 (M+1). 1H NMR (400 MHz, CDCl3) δ 1.19 (br d, J=6.2 Hz, 6H), 1.54 (s, 9H), 1.63-1.71 (br m, 1H), 1.83-1.97 (br m, 1H), 2.50-2.59 (m, 1H), 2.93 (dd, J=13, 4 Hz, 1H), 3.07-3.18 (br m, 1H), 3.41 (dd, J=9.9, 4.8 Hz, 1H), 3.58-3.68 (m, 2H), 3.72-3.89 (m, 2H), 4.20 (br d, J=12 Hz, 1H), 7.05-7.12 (m, 1H), 7.17-7.23 (m, 1H), 7.30-7.40 (m, 2H).

Provenance & Evidence