Trichloroacetimidic acid (S)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl ester → HCID 86610904, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 1.0 g (3.8 mmol) (3R,4S) tert-butyl-3-hydroxy-4-phenylpyrrolidine-1-carboxylate (Step B) and 3 g (7.6 mmol, 2 equiv) (S)-trichloroacetimidate (step C) in 40 mL dry heptanes and 10 mL dry methylene chloride under nitrogen atmosphere at 0° C. was added dropwise 0.092 mL (0.8 mmol, 0.2 equiv) HBF4-dimethyl ether complex. The resulting reaction mixture was stirred at 0° C. for 24 hr. The volatiles were removed under vacuum and the residue dissolved in 10 mL methylene chloride and purified by column chromatography on silica gel eluting with hexanes/EtOAc (8/2) to afford a mixture of two products. This mixture was further purified by preparative HPLC on ChiralPak OD column eluting with heptanes/ethanol (98/2) to obtain the minor isomer (epimeric at the benzylic methyl position) and the title compound. 1H-NMR (CDCl3): (rotamers): δ: 1.43-45 (2d, 3H, 6.5 Hz), 1.49-1.52 (2s, 9H), 3.3-3.5 (m, 3H), 3.73-3.97 (m, 3H), 4.53 (q, 1H, 6.5 Hz), 7.06-7.09 (m, 2H), 7.20-7.25 (m, 3H), 7.55 (m, 2H), 7.74 (s, 1H), 7.75 (s, 2H)ppm. MS: 447.9 (M-t-Bu)+ observed.

Provenance & Evidence