Cesium carbonate → Methyl 4-(4-chloro-2-fluorophenyl)-6-methylnicotinate

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl 4-chloro-6-methylnicotinate (660 mg, 3.56 mmol) and (4-chloro-2-fluorophenyl)boronic acid (620 mg, 3.56 mmol) in 1,4-dioxane (20 mL) was added cesium carbonate (3.48 g, 10.67 mmol). The reaction mixture was degassed with argon over a period of 5 min. Pd(Ph3P)4 (205 mg, 0.178 mmol) was added to the reaction mixture and heated to 80° C. for 16 h. The mixture was cooled to room temperature, diluted with water, and extracted with ethyl acetate (100 mL). The organic phase was washed with brine (2×50 mL), dried over Na2SO4, and concentrated under reduced pressure. The residue obtained was purified by silica gel chromatography to afford methyl 4-(4-chloro-2-fluorophenyl)-6-methylnicotinate (500 mg, 1.53 mmol, 43% yield) as a yellow liquid. LC/MS (ESI) m/e 280.0 [(M+H)+, calcd for C14H12ClFNO2 279.6]; LC/MS retention time (method C): tR=1.87 min.

Provenance & Evidence