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

Participants

Reaction Conditions

Reaction Steps

A flask charged with dimethyl t-butoxycarbonyl-methylphosphonate (0.21 mL, 1.06 mmol) in 2 mL of dry THF/DMPU (10:1) was cooled to −78° C. where 0.52 mL of n-butyl lithium (2.5 M hexane solution, 32 mmol) was added slowly via syringe. The reaction mixture was stirred at −78° C. for 10 minutes and then a solution of Compound 1D (173 mg, 0.43 mmol) in 2 mL of dry THF was added. After warming to room temperature and an additional 20 minutes of stirring, the reaction was quenched with 5 mL of water and passed through a solid phase extraction column (SPE). The column was washed with EtOAc (50 mL) and the collected eluant was evaporated to give crude product which was purified by flash chromatography (EtOAc/Hexanes; gradient 15% to 30%) to give 126 mg (60%) of product as a white solid. MS (electrospray): mass calculated for C27H30F3NO5, 505.21; m/z found 506.2, [M+H]+.

Provenance & Evidence