benzyl (2S)-2-amino-3,3-dimethylbutanoate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-(Dimethylaminopropyl)-N′-ethylcarbodiimide (2.298 g, 12 mmol) was added to a stirred mixture of (2R)-2-[2-(tert-butoxy)-2-oxoethyl]pent-4-enoic acid (2.13 g, 10 mmol tert-leucine benzyl ester (2.834 g, 11 mmol)(N. Moss et al., J. Med. Chem., 1996, 39, 2178), N-methylmorpholine (2.40 mL, 22 mmol) and 1-hydroxybenzotriazole hydrate (1.836 g, 12 mmol) in anhydrous dichloromethane (50 mL) under nitrogen at 0° C. The mixture was allowed to warm slowly to room temperature with the cooling bath in place. After 20 h, the mixture poured into ethyl acetate (250 mL) and washed with 5% aqueous citric acid (2×100 mL), saturated aqueous sodium bicarbonate (2×70 mL), brine (70 mL), dried (MgSO4), and concentrated under reduced pressure. The residual oil crystallised upon addition of pentane. The solid was filtered and dried to give tert-butyl (3R)-3-({[(1S)-2,2-dimethyl-1-(benzyloxycarbonyl)propyl]amino}carbonyl)hex-5-enoate (4.068 g, 97%), as a colourless solid. washed with 5% aqueous citric acid (2×100 mL), saturated aqueous sodium bicarbonate (2×70 mL), brine (70 mL) dried (MgSO4) concentrated under reduced pressure The residual oil crystallised upon addition of pentane The solid was filtered dried