Lithium Hexamethyldisilazide → HCID 59363800, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-(2-isobutoxyphenyl)ethanone (9.0 g, 0.047 mol) in tetrahydrofuran (150 mL) under N2 at −78° C. was added a 1.0 M solution of lithium hexamethyl disilazide in hexanes (100 mL, 2.2 eq) over 5 minutes. The reaction was stirred at −78° C. for 1 h. To the reaction solution was added 3-cyano-4-fluorobenzoyl chloride (8.6 g, 0.047 mmol) in tetrahydrofuran (28 mL) over 5 minutes at −78° C. The reaction mixture was then removed from the dry ice bath and allowed to stir for 1 h. The reaction was quenched with 1N HCl then partitioned between ethyl acetate and water. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The resulting solid was triturated with acetonitrile and filtered yielding 10.9 g (90%) of 2-fluoro-5-(3-(2-isobutoxyphenyl)-3-oxopropanoyl)benzonitrile and was submitted to the next step without further purification.

Provenance & Evidence