Hexamethyldisilazane → Rac-2-cyclohexyloxy-2-(3,4-dichloro-phenyl)-acetamide

Participants

Reaction Conditions

Reaction Steps

A solution of rac-cyclohexyloxy-(3,4-dichloro-phenyl)-acetic acid (Example 2; 364 mg, 1.20 mmol) in dichloromethane (10 mL) and N,N-dimethylformamide (one drop) cooled to 0° C. was treated with oxalyl chloride (2.0M solution in dichloromethane, 0.84 mL, 1.68 mmol). The reaction was stirred at 0° C. for 1 h, then 1,1,1,3,3,3-hexamethyldisilazane (0.90 mL, 4.20 mmol) was added and the cloudy mixture was stirred at 25° C. for 16 h. At this time, the reaction was quenched with methanol (10 mL), washed with an aqueous solution of 5% sulfuric acid (2×15 mL) and extracted with dichloromethane (3×10 mL). The combined organic extracts were washed with brine (1×10 mL), then were dried over magnesium sulfate, filtered and evaporated under reduced pressure. The product was purified by flash chromatography (Merck Silica gel 60, 230-400 mesh, 90/10 hexanes/ethyl acetate) to afford rac-2-cyclohexyloxy-2-(3,4-dichloro-phenyl)-acetamide (311 mg, 76% yield) as a colorless oil: FAB-HRMS m/e calcd for C14H17NCl2O2 (M+H)+ 302.0714, found 302.0728.

Provenance & Evidence