Tributylphosphine → (R)-4-butyl-1-[(S)-1-phenylethyl]pyrrolidin-2-one

Participants

Reaction Steps

To a solution of di-t-butyl azodicarboxylate (2.1 g, 9.1 mmol) in tetrahydrofuran (25 mL) under argon was added tributylphosphine (2.27 mL, 9.1 mmol). The mixture was stirred for 5 minutes and was added slowly to a solution of (R)-3-hydroxymethylheptanoic acid, (S)-1-phenylethylamide (1.84 g, 7.0 mmol) in dry THF (10 mL) at 0° C. The reaction was warmed up to rt and stirred overnight. Saturated NaHCO3 (100 mL) was added and the resulting mixture was extracted with CH2Cl2 (2×100 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated. The residue was purified by flash column chromatography (silica gel, 1:4 EtOAc/hexanes) to afford 1.4 g (82%) of (R)-4-butyl-1-[(S)-1-phenylethyl]pyrrolidin-2-one as a colorless oil: 1H NMR (CDCl3) δ 7.33 (m, 5 H), 5.48 (q, 1 H), 3.06 (t, 1 H), 2.92 (t, 1 H), 2.53 (q, 1 H), 2.06 (m, 2 H), 1.51 (d, 3 H), 1.20-1.46 (m, 6 H), 0.88 (t, 3 H). MS(ES) m/e 246 [M+H]+.

Provenance & Evidence