Phenol → Ethyl 6-chloro-4-phenoxynicotinate

Participants

Reaction Steps

To a solution of 196 mg (ca. 4 mmol) sodium hydride dispersion in mineral oil (ca. 50%) in 15 ml N,N-dimethylformamide a solution of 385 mg (4.09 mmol) phenol in 10 ml N,N-dimethylformamide was added dropwise at room temperature under argon. After 15 min. this solution was slowly added via cannula to a solution of 4,6-dichloro-nicotinic acid ethyl ester in 20 ml N,N-dimethylformamide at room temperature. After 2 h the reaction was quenched with 20 ml water. The mixture was extracted with 3 50-ml portions of ethyl acetate. The combined organic extracts were dried with sodium sulfate and concentrated. After drying in high vacuo at 50° C. and flash column chromatography 800 mg (70.4%) of the title compound was obtained as a white solid. As a side product 130 mg (11.4%) 4-chloro-6-phenoxy-nicotinic acid ethyl ester were also isolated.

Provenance & Evidence