Hexamethyldisilazane → Rac-2-(3,4-dichloro-phenyl)-2-(tetrahydro-pyran-4-yloxy)-acetamide

Participants

Reaction Conditions

Reaction Steps

A cooled (0° C.) solution of rac-(3,4-dichloro-phenyl)-[(tetrahydro-pyran-4-yloxy)]-acetic acid (Example 4; 441 mg, 1.45 mmol) in dichloromethane (10 mL) and N,N-dimethylformamide (one drop) was treated with oxalyl chloride (2.0 M solution in dichloromethane, 1.01 mL, 2.02 mmol). The reaction was stirred at 0° C. for 1 h, then 1,1,1,3,3,3-hexamethyldisilazane (1.10 mL, 5.06 mmol) was added and the resulting cloudy mixture was stirred at 25° C. for 16 h. 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 resulting residue was purified by flash chromatography (Merck Silica gel 60, 230-400 mesh, 70/30 hexanes/ethyl acetate) to provide rac-2-(3,4-dichloro-phenyl)-2-(tetrahydro-pyran-4-yloxy)-acetamide (278 mg, 63% yield) as a white solid, mp 81.9-83.6° C.; FAB-HRMS m/e calcd for C13H15NCl2O3 (M+H)+ 303.0428, found 303.0426.

Provenance & Evidence