(3aR,5R,7aS)-5-[(Benzyloxy)methyl]-7a-(2,4-difluorophenyl)hexahydro-1H-pyrano[3,4-c][1,2]oxazole → [(2R,4R,5S)-5-amino-2-[(benzyloxy)methyl]-5-(2,4-difluorophenyl)tetrahydro-2H-pyran-4-yl]methanol

Participants

Reaction Steps

(3aR,5R,7aS)-5-[(Benzyloxy)methyl]-7a-(2,4-difluorophenyl)hexahydro-1H-pyrano[3,4-c][1,2]oxazole (C21) (742 mg, 2.05 mmol) was mixed with acetic acid (6.8 mL). After addition of zinc powder (1.75 g, 26.7 mmol), the reaction mixture was stirred for 18 hours. Insoluble material was removed via filtration, and the solids were washed with ethyl acetate. The combined filtrates were washed with saturated aqueous sodium bicarbonate solution, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated under reduced pressure to provide the product as an opaque oil, which was used in the following reaction without additional purification. Yield: 748 mg, quantitative. LCMS m/z 364.4 (M+1). 1H NMR (400 MHz, CDCl3) δ 1.65 (ddd, J=14.0, 4.3, 2.6 Hz, 1H), 1.98-2.16 (br m, 1H), 2.24-2.41 (br m, 1H), 3.32-3.41 (m, 1H), 3.42-3.60 (m, 3H), 3.60-3.73 (br m, 1H), 3.82-3.92 (br m, 1H), 4.22 (dd, J=11.5, 2.3 Hz, 1H), 4.61 (AB quartet, upfield signals are broadened, JAB=12.1 Hz, ΔνAB=29 Hz, 2H), 6.83 (ddd, J=12.6, 8.6, 2.6 Hz, 1H), 6.92-7.05 (br m, 1H), 7.27-7.40 (m, 5H), 7.62-7.79 (br m, 1H).

Provenance & Evidence