p-Xylyl bromide → 4-[(tert-Butoxycarbonyl)amino]-2-(4-methylbenzyl)-butanoic acid

Participants

Reaction Conditions

Reaction Steps

To a solution containing LiHMDS (1.0M, 11.3 mL, 11 mmol) in 40 mL of THF under a nitrogen atmosphere at −78C was added a solution of 2-Oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (2.gg, 11 mmol) in 15 mL of THF dropwise over 5 minutes. After complete addition, the reaction was allowed to stir at −78° C. for 45 minutes, followed by the addition of a solution containing 4-methyl benzyl bromide (2.1 g, 11 mmol) in 15 mL of THF dropwise over 5 minutes. The reaction was allowed to stir at −78C for 1 hour then warmed to 0 C and stirred for 1 hour. The mixture was quenched with 36 mL of 3M LiOH and allowed to stir at room temperature overnight. The reaction was diluted with water and washed with ether. The aqueous phase was acidified with 1N HCl and extracted with DCM. The organic phase was dried over magnesium sulfate. Filtration and removal of solvent gave 4-tert-Butoxycarbonylamino-2-(4-methylbenzyl)-butyric acid (1.61 g, 49%.) LCMS (APCI−) m/z 306 [M-Boc-H]−; Rt: 2.14 min.

Provenance & Evidence