Lithium (trimethylsilyl)acetylide → 2-((R)-3-hydroxy-1,1-dimethyl-3-trifluoromethyl-6-trimethylsilanylhex-5-ynyl)benzamide

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Reaction Steps

To a stirred, ice-cooled, solution of (trimethylsilyl)acetylene (72.6 mL, 514 mmol) in 500 mL of ethylene glycol dimethyl ether was added n-butyllithium (185 mL of 2.5 M solution in hexanes, 462 mmol). The reaction mixture, which turned from a colorless to a yellowish solution, was stirred for 50 minutes to give a solution of 462 mmol of lithium (trimethylsilyl)acetylide. A stirred solution of 2-[1,1-dimethyl-2-((R)-2-trifluoromethyloxiranyl)ethyl]benzamide (26.5 g, 92.3 mmol) in ethylene glycol dimethyl ether (250 mL) was cooled to −30° C. Dibutylmagnesium (50.8 mL of 1 M solution in heptane, 50.8 mmol) was added and the mixture stirred for 45 minutes. The above solution of lithium (trimethylsilyl)acetylide was added and the stirring continued at −20° C. After 5 minutes, cooling bath was removed and the reaction mixture was stirred for 3 hours and 15 minutes. The reaction was quenched with 600 mL of saturated ammonium chloride solution and extracted with four 250 mL portions of ethyl acetate. The combined organic extracts were washed with two 250 mL portions of brine, dried over anhydrous sodium sulfate, and the solvent removed in vacuo to give 2-((R)-3-hydroxy-1,1-dimethyl-3-trifluoromethyl-6-trimethylsilanylhex-5-ynyl)benzamide as brownish oil (27 g).

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