Acetone → 3-Methyl-1-phenyl-3-[(trimethylsilyl)oxy]butan-1-one

Participants

Reaction Conditions

Reaction Steps

A flask is charged with THF (1 L), cooled to −50° C., and treated with lithium diisopropylamide (LDA) (1.05 L, 1.89 mol, 1.1 equiv, 1.8M in THF/heptane/ethylbenzene). The reactor contents are then treated with acetophenone (200 mL, 1.71 mol, 1.0 equiv) at a rate to maintain the batch at about −50° C. The reaction mixture is stirred at about −50° C. for 30 minutes then treated with acetone (151 mL, 2.06 mol, 1.2 equiv) at a rate to maintain the mixture at about −50° C. The reaction mixture is stirred at about −50° C. for 1 hour then treated with water (1 L) and heptane (500 mL). The reaction mixture is allowed to warm to 25° C., and the resultant organic phase is collected and washed with water (400 mL). The organic phase is concentrated to an oil and treated with a solution of imidazole (233.4 g, 3.43 mol, 2.0 equiv) and DMF (600 mL). The resultant solution is treated with chlorotrimethylsilane (217.6 mL, 1.71 mol, 1.0 equiv) at a rate to maintain the reaction mixture at no more than 35° C. The reaction mixture is stirred at 25° C. for 1 hour, and diluted with heptane (600 mL) and water (1 L). The resultant organic phase is collected, washed with water (3×500 mL), and concentrated. The resultant oil is then vacuum distilled at 1-3 mm Hg (product distills at 83-88° C.) to provide 2 as a yellow liquid. Yield: 160.3 g, 37%.

Provenance & Evidence