tert-Butyl bromoacetate → [3-[[(1,1-Dimethylethyloxycarbonyl)methyl]amino]propyl]carbamic acid phenylmethyl ester

Participants

Reaction Steps

A solution of (3-aminopropyl)carbamic acid phenylmethyl ester (7.08 g, 34 mmol) and N,N-diisopropylethylamine (4.5 mL, 26 mmol) in anhydrous dimethylformamide (100 mL) under nitrogen was cooled to 10° C. and treated with t-butyl bromoacetate (2.80 mL, 17 mmol) over 5 minutes. After one hour the bath was removed and the reaction mixture was stirred overnight, poured into water (500 mL), and made basic (pH 12) with 2.5N sodium hydroxide solution. The aqueous layer was extracted with dichloromethane (2×250 mL), which was dried over sodium sulfate and concentrated in vacuo with heat to remove dimethylformamide. The residue was purified by flash chromatography (9 cm diameter, gradient elution with 2.5-3.5% methanol in dichloromethane) to yield [3-[[(1,1-dimethylethyloxycarbonyl)methyl]amino]propyl]carbamic acid phenylmethyl ester as a pale yellow oil (4.50 g, 82%); 1H NMR (CDCl3, 200 MHz): δ 7.35 (m, 5H), 5.43 (br s, NH), 5.09 (s, 2H), 3.35-3.24 (m, 4H), 2.68 (t, J=6.5 Hz, 2H), 1.68 (p, J=6.5 Hz, 2H), 1.46 (s, 9H).

Provenance & Evidence