Ammonium Chloride → rel-[(3R,3aR,5R)-5-cyclopropyl-3,3a,4,5-tetrahydro-7H-pyrano[3,4-c][1,2]oxazol-3-yl]methanol

A solution of methyl rel-(3R,3aR,5R)-5-cyclopropyl-3,3a,4,5-tetrahydro-7H-pyrano[3,4-c][1,2]oxazole-3-carboxylate (C36) (3.30 g, 14.6 mmol) in ethanol (30 mL) and tetrahydrofuran (29 mL) was cooled to 0° C. and treated with sodium borohydride (831 mg, 22.0 mmol). The reaction mixture was allowed to warm to room temperature and stir for 20 minutes at that temperature, then was poured into saturated aqueous ammonium chloride solution. The mixture was extracted with ethyl acetate, and the combined organic layers were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated in vacuo. Chromatographic purification on silica gel (Eluent: 60% ethyl acetate in heptane) afforded the product as an oil. Yield: 1.95 g, 9.89 mmol, 68%. LCMS m/z 198.1 [M+H+]. 1H NMR (400 MHz, CDCl3) δ 4.67 (br d, J=13.3 Hz, 1H), 4.24-4.31 (m, 1H), 4.13 (d, J=13.3 Hz, 1H), 3.96-4.04 (m, 1H), 3.72 (ddd, J=12.3, 8.8, 3.5 Hz, 1H), 3.38 (ddd, J=10.9, 10.9, 6.6 Hz, 1H), 2.79-2.87 (m, 1H), 2.25 (dd, J=12.9, 6.6 Hz, 1H), 1.80-1.95 (m, 1H), 1.63-1.74 (m, 1H), 0.88-0.99 (m, 1H), 0.50-0.68 (m, 2H), 0.38-0.46 (m, 1H), 0.21-0.29 (m, 1H).

1. extractionThe mixture was extracted with ethyl acetate
2. washthe combined organic layers were washed with saturated aqueous sodium chloride solution
3. dry with materialdried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customChromatographic purification on silica gel (Eluent: 60% ethyl acetate in heptane)

ORD record

ord-4eccea4da3d14be391c1955cac126447

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09403846B2