Diisopropylethylamine → N-tert-butyl acetyl-(S)-leucine methyl ester

Participants

Reaction Conditions

Reaction Steps

A solution of bromo-tert-butyl acetate (44.4 mL, 0.275 mol), (S)-leucine methyl ester hydrochloride (50 g, 0.275 mol) and diisopropylethyl amine (191 mL, 1.1 mol) in acetonitrile (400 mL) was stirred at room temperature for 16 hrs and heated at 60° C. for 4 hrs. After completion of the reaction (TLC, hexane-ethyl acetate, 9:1) a small aliquot (5 mL) was taken out and acetonitrile was removed under reduced pressure. Ethyl acetate (100 mL) was added and the solution was washed with water (2×100 mL), 10% aqueous citric acid (100 mL) and water (100 mL). The ethyl acetate extract was dried over sodium sulfate, evaporated under reduced pressure and chromatographed over silica gel column. Elution with 5% ethyl acetate in hexane gave pure N-tert-butyl acetyl-(S)-leucine methyl ester (2) as an oil, [α]D25 -17.2 (c, 2.9, MeOH); 1H NMR (CDCl3): 0.88 (3H, d, J=6.6 Hz), 0.89 (3H, d, J=6.6 Hz), 1.42 (9H, s), 1.48 (2H, m), 1.70 (1H, apparent hept, J=6.6 Hz), 3.24 (2H, ABq, J=18 Hz), 3.29 (1H, t, J=7.2 Hz), 3.68 (3H, s); 13C NMR (CDCl3): 22.34 (CH3), 22.65 (CH3), 24.81 (CH), 28.06 (C(CH3)3), 42.44 (CH2), 49.86 (CH2), 51.74 (OCH3), 59.22 (CH), 81.26 (C), 170.87 (CO), 175.43 (CO).

Provenance & Evidence