Sodium Hydroxide → (s)-3-[1-(2,4-Dichlorophenyl)-ethylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Steps

Stir a mixture of (S)-3-aminopyrrolidine-1-carboxylic acid tert-butyl ester (10.4 g, 55.7 mmol) and 2,4-dichloroacetophenone (10.5 g, 55 mmol) in dry toluene (400 mL) at 110° C. for 48 h. Concentrate and dissolve the residue in methanol (160 mL), add sodium borohydride (3.37 g, 89 mmol) slowly and stir for 20 min. Add 1 N sodium hydroxide (200 mL) and extract with diethyl ether. Combine the organic layers, wash with water, dry (magnesium sulfate), concentrate and chromatograph on silica gel, eluting with 0:100 to 40:60 ethyl acetate:2-methylpentane to give (S)-3-[1-(2,4-dichlorophenyl)-ethylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (5.6 g, 28%). 1H NMR (300 MHz, CDCl3) δ 7.41-7.51 (1H, m), 7.34 (1H, s), 7.24 (1H, dd, J=8.38, 1.98 Hz), 4.21-4.36 (1H, m), 3.42-3.57 (2H, m), 3.21-3.33 (1H, m), 3.04-3.15 (1H, m), 2.88-3.03 (1H, m), 1.96-2.05 (1H, m), 1.63-1.72 (1H, m), 1.37-1.47 (9H, m), 1.30 (3H, dd, J=6.59, 1.51 Hz), MS (ES): m/z=359[M+].

Provenance & Evidence