Protection of Side Chain Functions

Abstract

A sample of N-tert-butyloxycarbonyl-l-serine (20.5 g, 100 mmol) is dissolved in dimethylformamide [3] (500 ml), the solution is cooled to 0 °C and treated with sodium hydride [4] (8.2 g 65% material, 220 mmol). When no more gas evolves benzyl bromide [5] (18.8 g = 13.1 ml, 110 mmol) is added and the mixture is stirred at 25–30 °C for about 5 hours. The solvent is removed in vacuo at 40 °C bath temperature, the residue dissolved in water (500 ml) and the solution extracted with ether (twice, 200 ml each time). The aqueous layer is acidified to pH 3.5 with 3 N HC1 and then extracted with ethyl acetate (five times, each time with 200 ml). The extracts are pooled, washed with water (twice, 200 ml each time) and dried over anhydrous MgSO₄. The solvent is removed in vacuo and the residue, a colorless oil, dissolved in ether (300 ml). Cyclohexylamine (9.0 g = 10.4 ml, ca 90 mmol) is added to the solution: the cyclohexylammonium salt of N-tert-butyloxycarbonyl-0-benzyl-l-serine precipitates. It is collected on a filter and thoroughly washed with ether. After recrystallization from ethyl acetate the product (about 22 g, 56%) melts at 159–160°C; [α] ²⁵_D −29° (c 1, methanol). On elemental analysis values close to the ones calculated for C, H and N, are obtained.