1-Bromo-4-phenylmethoxybenzene → methyl (2S)-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-5-oxo-5-{4-[(phenylmethyl)oxy]phenyl}pentanoate

Participants

Reaction Conditions

Reaction Steps

To a solution of commercially available (Sigma Aldrich Ltd.) 1-bromo-4-[(phenylmethyl)oxy]benzene (390 mg, 1.48 mmol) in dry THF (2 ml) at −78° C., under nitrogen atmosphere, was added dropwise n-butyllithium 1.6M solution in hexanes (0.88 ml, 1.4 mmol). The resulting suspension was stirred at −78° C. for 40 minutes and then it was added dropwise to a solution of 1-(1,1-dimethylethyl) 2-methyl (2S)-5-oxo-1,2-pyrrolidinedicarboxylate (D1, 300 mg, 1.23 mmol) in dry THF (2.4 ml) previously cooled to −78° C. The mixture was stirred at −78° C. for 40 minutes and at −40° C. for 1 h, then it was quenched at −40° C. with a saturated aqueous ammonium chloride solution. The mixture was diluted with water and extracted with ethyl acetate. The organic phase was then washed with brine, dried (Na2SO4), and evaporated under vacuo to give the crude material, which was then purified by chromatography on silica gel eluting with cyclohexane:ethyl acetate (95:5), thus affording the title compound as a white solid (170 mg, 32%); Rf (cyclohexane:ethyl acetate 8:2): 0.30; 1H NMR (300 MHz, CDCl3) δ(ppm): 7.95 (d, 2H), 7.50-7.33 (m, 5H), 7.03 (d, 2H), 5.20 (bs, 1H), 5.15 (s, 2H), 4.45-4.35 (m, 1H), 3.78 (s, 3H), 3.15-2.95 (m, 2H), 2.36-2.26 (m, 1H), 2.16-2.02 (m, 1H), 1.45 (s, 9H).

Provenance & Evidence