Trimethylsilyldiazomethane → [4-(5-tert-Butyl-3-ethynyl-4-isopropoxy-2-methyl-phenylethynyl)-phenyl]-acetic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

Anhydrous tetrahydrofuran (3 mL) was added to a 2M solution of trimethylsilyl diazomethane in hexanes (0.37 mL, 0.74 mmol) and the resulting reaction mixture was cooled to −78° C. A solution of 1.6M n-butyl lithium in hexanes (0.5 mL, 0.8 mmol) was added followed, after 30 minutes, by a solution of [4-(5-tert-butyl-3-formyl-4-isopropoxy-2-methyl-phenylethynyl)-phenyl]-acetic acid methyl ester (Intermediate 144, 0.2 g, 0.49 mmol) in anhydrous tetrahydrofuran and the resulting reaction mixture was stirred at −78° C. for 1 h and at 0° C. for 40 minutes. The reaction mixture was then quenched with saturated aqueous ammonium chloride solution and extracted with diethyl ether. The organic phase was washed with brine, dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to a residue that was subjected to flash column chromatography over silica gel (230-400 mesh) using 2.5-4% ethyl acetate in hexane as the eluent followed by preparative normal phase HPLC using 5% ethyl acetate in hexane as the mobile phase to afford the title product as a colorless oil (0.023 g, 11.6%). 1H NMR (300 MHz, CDCl3): δ 7.49 (d, 2H, J=8.0 Hz), 7.44 (s, 1H), 7.26 (d, 2H, J=8.0 Hz), 5.76 (heptet, 1H, J=6.1 Hz), 3.70 (s, 3H), 3.64 (s, 2H), 3.58 (s, 1H), 2.58 (s, 3H), 1.39 (s, 9H), 1.31 (d, 6H, J=6.1 Hz).

Provenance & Evidence