Tetrabutylammonium Fluoride → (2R,4R)-tert-butyl 2-(3-cyano-5-fluorophenyl)-4-hydroxypyrrolidine-1-carboxylate

Participants

Reaction Steps

To a solution of (4R)-tert-butyl 4-((tert-butyldimethylsilyl)oxy)-2-(3-cyano-5-fluorophenyl)pyrrolidine-1-carboxylate (I-12) (2.7 g, 6.4 mmol) in THF (25 mL) at room temperature was added TBAF (7.1 mL of a 1.0 M solution in THF, 7.0 mmol). The mixture was stirred at room temperature for 1 hour then concentrated. The mixture was purified by column chromatography on silica gel with EtOAc/hexanes gradient as eluant to yield the desired isomer (2R,4R)-tert-butyl 2-(3-cyano-5-fluorophenyl)-4-hydroxypyrrolidine-1-carboxylate (I-13A) and (2S,4R)-tert-butyl 2-(3-cyano-5-fluorophenyl)-4-hydroxypyrrolidine-1-carboxylate (I-13B). 1H NMR (400 MHz, CDCl3) δ 7.41 (s, 1 H), 7.35-7.26 (m, 1 H), 7.24-7.16 (m, 1 H), 4.89 (d, J=48.8 Hz, 1 H), 4.56-4.50 (m, 1 H), 3.85-3.70 (m, 1 H), 3.66-3.55 (m, 1 H), 2.59 (bs, 1 H), 2.00-1.90 (m, 1 H), 1.45 (bs, 3 H), 1.22 (bs, 6 H). MS m/z 304.1 (M+23)+.

Provenance & Evidence