(3aR,4S,6aS)-6a-(3-chloro-2,4-difluorophenyl)-4-((trityloxy)methyl)hexahydrofuro[3,4-c]isoxazole → ((2S,3R,4S)-4-Amino-4-(3-chloro-2,4-difluorophenyl)-2-((trityloxy)methyl)tetrahydrofuran-3-yl)methanol

Participants

Reaction Steps

Zinc (2.75 g, 42.1 mmol) was added in one portion to a stirred suspension of (3aR,4S,6aS)-6a-(3-chloro-2,4-difluorophenyl)-4-((trityloxy)methyl)hexahydrofuro[3,4-c]isoxazole (4.5 g, 8.43 mmol) in acetic acid (15 mL) at RT. An exotherm was noted. The mixture was stirred at RT overnight. The zinc was removed by filtration through Celite® washing with methanol. The filtrate was evaporated and the residue was partitioned between DCM and saturated aqueous NaHCO3. The mixture was filtered through Celite® again—washing with DCM and water. The layers were separated and the aqueous layer was further extracted with DCM (×3). The combined extracts were dried by passing through a hydrophobic frit and evaporated to give the title compound (4.38 g). 1H NMR (400 MHz, CDCl3) δ ppm: 2.61-2.71 (m, 1 H) 3.23-3.32 (m, 2 H) 3.68 (dd, J=12.04, 5.32 Hz, 1 H) 3.91 (dd, J=12.10, 4.28 Hz, 1 H) 3.96 (dd, J=9.23, 2.63 Hz, 1 H) 4.28-4.37 (m, 2 H) 6.94-7.01 (m, 1 H) 7.20-7.34 (m, 9 H) 7.38-7.53 (m, 7 H.

Provenance & Evidence