Pyridine → HCID 11351286, compound

Participants

Reaction Steps

To a solution of 200 mg intermediate step E (0.47 mmol) in 3 mL dry methylene chloride at 0° C. was added 0.097 mL pyridine (1.18 mmol) followed by 0.089 mL acetic anhydride (0.94 mmol). The reaction mixture was stirred for 6 hr at ambient temperature then the volatiles were removed under vacuum. The residue was partitioned between 2N aq. NaOH (5 mL) and methylene chloride (10 mL). The layers were separated and the aqueous layer extracted with methylene chloride (2×5 mL). The combined organic extracts were dried over sodium sulfate, filtered and solvent evaporated under vacuum. The resulting material was purified by preparative TLC eluting with methylene chloride/methanol (9/1). The resulting material was further purified by prep HPLC on Chiralpak AD column eluting with heptanes/ethanol (97/3) to afford a minor faster moving isomer A (3R,4S)-1-acetyl-3-({(1S)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}oxy)-4-phenylpyrrolidine and the title compound. 1H-NMR (CDCl3) rotamers: δ: 1.45 (t, 3H, 6.5 Hz), 2.15 (2s, 3H) 3.38-3.63 (m, 3H), 3.85-4.03 (m, 3H), 4.58 (m, 1H), 7.1 (m, 2H), 7.25 (m, 3H), 7.61 (s, 2H), 7.78 (s, 1H)ppm. MS: 446 (MH)+ observed.

Provenance & Evidence