Acetic Acid → Dimethyl((3S)-4-phenyl-3-(Boc-amino)-2-oxobutyl)phosphonate

Participants

Reaction Conditions

Reaction Steps

A solution of dimethyl methylphosphonate (3.10 mL, 28.60 mmol, 8.0 eq) in anhydrous THF (30 mL) was cooled to −78° C. and 2.5 N n-BuLi (2.70 mL, 28.60 mmol, 8.0 eq) was added dropwise. After addition, the solution was stirred at −78° C. for 30 min and then a solution of compound 6 (1.00 g, 3.58 mmol, 1.0 eq) in anhydrous THF (20 mL) was added slowly. The resulting mixture was stirred at −78° C. for 1 h and then at ambient temperature for 1 h. The solution was acidified with 10% AcOH (20 mL), extracted with EtOAc (3×50 mL). The extract was washed with 10% NaHCO3, brine, dried over anhydrous MgSO4 and evaporation of the solvent gave a crude residue, which was subjected to column chromatography on silica gel elution with 100% EtOAc afforded the compound dimethyl [(3S)-4-phenyl-3-[(tert-butyloxycarbonyl)amino]-2-oxobutyl]-phosphonate 7 as a clear oil (0.797 g, 59%), which crystallizes in hexane as a white solid; mp 78-81° C. (lit.1 mp 76-78° C.); Rf 0.38 (EtOAc); 1H NMR (300 MHz, CDCl3) δH 1.38 (9H, s, (CH3)3), 2.84-3.32 (4H, m), 3.74 and 3.78 (6H, 2xs, 2xOMe), 4.55 (1H, q, J=8.4 Hz, —CH—), 5.28 (1H, d, J=8.4 Hz, —NH—), and 7.16-7.32 (5H, m, Ar—H).

Provenance & Evidence