tert-Butyl Dimethylphosphonoacetate → 3-[3-(1-Ethyl-4,4,6-trimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-7-yl)-4-trifluoromethoxy-phenyl]-acrylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

A flask charged with 0.23 mL (2.5 mmol) of dimethyl t-butoxycarbonyl-methylphosphonate in 8.75 mL of dry THF/DMPU (10:1). The flask was cooled to −78° C. where 1.78 mL (0.9 mmol, 2.5M hexanes) of n-butyl lithium was added slowly via syringe. The reaction mixture was stirred at −78° C. for 10 minutes and then a solution of 0.35 g (0.86 mmol) of Compound 14E in 3 mL of dry THF was added. After warming to room temperature and an additional 20 minutes of stirring, the reaction was quenched with 3 mL of water and then partitioned with 10 mL of saturated ammonium chloride and 20 mL of ethyl acetate, The water layer was further extracted with ethyl acetate (2×15 mL) and the combined organic layers were then washed with brine (10 mL), dried over magnesium sulfate, filtered and excess solvent was removed on the rotary evaporator. The crude product was purified by flash chromatography (3.5:1 EtOAc/Hexanes) to give 0.16 g (41%) of the product as a white solid. MS (electrospray): mass calculated for C23H22F3NO5, 449.15; m/z found 450, [M+H]+.

Provenance & Evidence