Cesium carbonate → Methyl 4-chloro-2-methylpyridine-3-carboxylate

Participants

Reaction Steps

To a solution of methyl 2,4-dichloronicotinate (10.0 g, 48.5 mmol) in a solvent mixture of 1,4-dioxane (400 mL) and water (40 mL) was added trimethylboroxine (6.79 mL, 48.5 mmol) followed by PdCl2(dppf)-CH2Cl2 adduct (1.982 g, 2.427 mmol) and cesium carbonate (31.6 g, 97 mmol). The reaction mixture was degassed with argon for 5 minutes. The reaction mixture was heated to reflux for 8 h. The reaction mixture was cooled to room temperature and filtered through diatomaceous earth (Celite®). The bed was washed with ethyl acetate and the combined filtrate was concentrated under reduced pressure to afford the crude product which was purified by silica gel column chromatography (gradient of ethyl acetate and petroleum ether) to afford methyl 4-chloro-2-methylnicotinate (5.20 g, 28 mmol, 58% yield) as a yellow liquid. LC/MS (ESI) m/e 185.7 [(M+H)+, calcd for C8H8ClNO2 185.6]; LC/MS retention time (method G): tR=1.90 min.

Provenance & Evidence