Methanol → (S)-1-Benzyl-5-hydroxymethyl-2-pyrrolidinone

Participants

Reaction Steps

A solution of (S)-5-oxo-1-(phenylmethyl)-2-pyrrolidinecarboxylic acid methyl ester (132 g, 0.556 mol) in 600 mL of t-butanol was cooled to ca. 18° C. Sodium borohydride (41 g, 1.12 mol) was added in one portion. To the suspension was added over 45 min 425 mL of methanol. The reaction was kept at 15° C. during the addition, during which time hydrogen gas was evolved. After the addition, the mixture was kept at 20° C. until hydrogen evolution had subsided, and was allowed to stand at room temperature overnight. The solvents were removed on a rotary evaporator, and the residue was dissolved in 1 L of water and acidified to pH 7.5 with 2N HCl. The mixture was extracted with methylene chloride and the combined extracts were washed with 2N HCl and brine, and dried over Na2SO4. Evaporation of the solvent afforded 96.3 g of crude product, which was recrystallized once from toluene to give 89.5 g (77% yield) of (S)-5-(hydroxymethyl)-1-(phenylmethyl)-2-pyrrolidinone as a white solid, mp 82°-4° C. (toluene). 1H NMR (CDCl3) δ 1.92 and 1.94 (dd, J=6.5 Hz, 1 H, OH), 1.96-2.11 (m, 2 H, CH2), 2.36-2.61 (m, 2 H, COCH2), 3.48-3.78. (m, 3 H, CH2O and CH), 4.29 and 4.81 (AB, Jgem =15 Hz, 2 H, CH2Ph), 7.26-7.35 (m, 5 H, phenyl). [α]25D =+116° (c 1.07, methanol). Anal. Calcd for C12H15NO2 : C, 70.22; H, 7.37; N, 6.75. Found: C, 70.06; H, 7.41; N 6.75.

Provenance & Evidence