Dimethylformamide → 5-Butyl-2-chloro-nicotinic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

Phosporous oxychloride (4.76 ml, 51 mmol) was added within 10 minutes to an ice cold solution of (E)-2-cyano-oct-2-enoic acid methyl ester (4.65 g, 26 mmol) in DMF (12 ml) under an argon atmosphere. The reaction mixture was stirred for 14 h at 80° C. and poured onto ice water. After 3 h the mixture was extracted two times with dichloromethane, the combined extracts were washed with ice water and dried over sodium sulfate. Removal of the solvent under reduced pressure left a brown oil which was purified by column chromatography (silica gel, isopropyl acetate/heptane) to give 5-butyl-2-chloro-nicotinic acid methyl ester (1.01 g, 4.4 mmol; 17%) as yellow oil. MS: m/e=227.0 [M+H+].

Provenance & Evidence