HCID 70558999, compound → HCID 70558117, compound

Participants

Reaction Conditions

Reaction Steps

(3aR,4S,6aS)-4-(fluoromethyl)-6a-(2-fluorophenyl)hexahydrofuro[3,4-c]isoxazole (62.20 g, 257.14 mmol) was dissolved in acetic acid (540 mL) and the solution was cooled to 0° C. Zinc dust (168.14 g, 2571.4 mmol) was added over 15 mins. The reaction temperature rose from 8° C. to 16° C. The ice bath was removed after addition and the reaction mixture was allowed to warm up to RT. Internal temperature increased to 40° C. and gradually went down to 24° C. The reaction was stirred at RT for 16 h. The reaction mixture was filtered through celite, and washed with 1.5 L of EtOAc. The solvent was evaporated and the crude product was dissolved in chloroform (600 mL), and ammonia (28% aq., 240 mL) was added slowly using a dropping funnel. Internal temperature rose to 40° C. The layers were separated, and the aqueous layer was further extracted with chloroform (3×250 mL). The combined organic extracts were dried over anhydrous MgSO4 and evaporated to afford the title compound (63.00 g, 100%) which was used in the subsequent step without further purification. 1H-NMR (400 MHz, CDCl3) δ ppm 2.39-2.86 (m, 4H) 3.81 (dd, J=11.87, 4.55 Hz, 1H) 3.94 (dd, J=9.09, 3.03 Hz, 1H) 4.07 (dd, J=12.13, 4.04 Hz, 1H) 4.25 (d, J=9.09 Hz, 1H) 4.40-4.68 (m, 3H) 7.09 (ddd, J=12.57, 8.15, 1.26 Hz, 1H) 7.17 (td, J=7.58, 1.26 Hz, 1H) 7.28-7.34 (m, 1H) 7.49 (td, J=8.08, 1.77 Hz, 1H)

Provenance & Evidence