Glycine methyl ester hydrochloride (8) (9.4g, 75.0mmol) was dissolved in dry dichloromethane (150ml) under argon, and then treated with triethylamine (26.1ml, 187.0mmol). The resulting thick white mixture was stirred for 10min., then cooled in an ice-salt bath, and bromoacetyl bromide (9.8ml, 112.0mmol) added dropwise over 20min. The mixture was then allowed to stir for a further 2h at 0degC, then washed sequentially with water (200ml), 2M hydrochloric acid (150ml), saturated sodium bicarbonate (150ml) and water (200ml). The organic solution was dried over magnesium sulphate and then concentrated under reduced pressure. The residue was purified by chromatography on silica gel (petroleum ether/ethyl acetate 2:1) to give the N-bromoacetyl-glycine methyl ester (10) (6.87g, 44%) as a pale yellow solid, m.p. 59degC.

Proton Nmr deltaH (300MHz, CDCl3) 3.72(3H, s, OCH3), 3.87(2H, s, CH2Br), 4.02(2H, d, J=5.5Hz, 2xH-2), 7.09(1H, br. s, NH); Vmax: 3262, 1750, 1652cm^-1; m/z (NH3, CI) 229/227(M+NH4⁺, 100%). Found [M+NH4]⁺ 227.0027, C5H12N2O3Br requires 227.0032.

Preparation of N-Bromoacetyl-L-alanine Methyl Ester (11)

L-Alanine methyl ester hydrochloride (9) (6.98g, 50.0mmol) was dissolved in dry dichloromethane (250ml) under argon, and treated with triethylamine (18ml, 130.0mmol). The resulting thick white mixture was stirred for 10min., then cooled in an ice-salt bath, and bromoacetyl bromide (5.3ml, 60.0mmol) added dropwise over 20min. The mixture was then allowed to stir for a further 3.5h at 0degC, then washed sequentially with water (150ml), 2M hydrochloric acid (150ml), saturated sodium bicarbonate (150ml) and water (150ml). The organic solution was then dried over magnesium sulphate and concentrated under reduced pressure. The crude product was purified by chromatography on silica gel (petroleum ether/ethyl acetate 2:1) to give N-bromoacetyl-L-alanine methyl ester (11) (6.95g, 62%) as a pale yellow solid, m.p. 58degC, [alpha]D -13deg (c 1.1, dichloromethane).

Proton Nmr deltaH (300MHz, CDCl3) 1.42(3H, d, J=7.5Hz, CHCH3), 3.75(3H, s, OCH3); 3.86(2H, apparent s, CH2Br), 4.59-4.50(1H, m, H-2), 7.01(1H, br. s, NH); Vmax: 3299, 1748, 1661, 1641cm^-1; m/z (NH3, CI) 243/241(M+NH4⁺, 98%), 224/222(M+H⁺, 9%), 243(100%), 163(25%). Found [M+H]⁺ 223.9926, C6H11NO3Br requires 223.9922.