Phosphorus pentachloride → methyl 6-chloro-5-cyano-2-methylnicotinate

Participants

Reaction Conditions

Reaction Steps

A mixture of methyl-5-cyano-6-hydroxy-2-methylnicotinate (2.0 g, 10.41 mmol), POCl3 (40 mL) and PCl5 (1.08 g, 5.2 mmol) was heated to 110° C. for 24 h. The reaction mixture was concentrated under reduced pressure and quenched with ice-water. The organic product was extracted with EtOAc and the organic layer was washed with H2O and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 60-120 mesh, eluent 10-15% EtOAc in petroleum ether) to afford methyl 6-chloro-5-cyano-2-methylnicotinate (1.5 g, yield 68%). 1H NMR (300 MHz, CDCl3) δ 8.48 (s, 1H), 3.96 (s, 3H), 2.90 (s, 3H).

Provenance & Evidence