tert-Butyl bromoacetate → (R)-tert-butyl 4-((S)-4-benzyl-2-oxooxazolidin-3-yl)-3-(biphenyl-4-ylmethyl)-4-oxobutanoate

Participants

Reaction Conditions

Reaction Steps

A stirred solution of (S)-4-benzyl-3-(3-(biphenyl-4-yl)propanoyl)oxazolidin-2-one (intermediate 12: 5.01 g, 13.00 mmol) in THF (180 mL) is cooled to −73.8° C., and 1M THF solution of sodium hexamethyldisilylamide (14.30 mL, 14.30 mmol) is added during 5 minutes. After 30 minutes, a solution of tert-butyl bromoacetate (2.495 mL, 16.90 mmol) in THF (20 mL) is added dropwise during 5 minutes. The solution is stirred at −74° C. for 1 hour, and the reaction is quenched with saturated aqueous NH4Cl (100 mL), and warmed up to ambient temperature. The precipitated solid is filtered off and washed with ethyl acetate (50 mL). The organic phase is separated, washed with brine, dried over MgSO4, and concentrated under reduced pressure. The obtained residue is suspended in MeOH (70 mL) and then filtered to collect the solid (5.9 g) as a mixture of the desired product and the starting material. The mixture is purified by flash column chromatography on 120 g of silica gel (heptane/EtOAc=90:10 to 50:50) to give (R)-tert-butyl 4-((S)-4-benzyl-2-oxooxazolidin-3-yl)-3-(biphenyl-4-ylmethyl)-4-oxobutanoate (2.40 g, 37%). HPLC retention time=1.74 minutes (condition B); MS=499.4 (m+); 443.4 (m-tBu+1; 100%); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.41 (s, 9H) 2.42 (dd, J=16.67, 4.04 Hz, 1H) 2.71 (ddd, J=16.55, 13.26, 9.60 Hz, 2H) 2.87 (dd, J=16.93, 10.86 Hz, 1H) 3.04 (dd, J=13.14, 6.32 Hz, 1H) 3.32 (dd, J=13.39, 3.03 Hz, 1H) 3.92 (t, J=8.34 Hz, 1H) 4.07 (dd, J=8.97, 2.15 Hz, 1H) 4.48-4.58 (m, 2H) 7.20-7.30 (m, 3H) 7.30-7.36 (m, 5H) 7.42 (t, J=7.58 Hz, 2H) 7.52 (d, J=8.1 Hz, 2H) 7.56 (d, J=7.8 Hz, 2H).

Provenance & Evidence