Diethyl Carbonate → Ethyl 2-(2-chloropyridin-4-yl)acetate

Participants

Reaction Conditions

Reaction Steps

In a 1000 mL round-bottom flask, diisopropylamine (80.21 mL, 567.5 mmol) was combined with THF (250 mL) and cooled to −78° C. Butyllithium (227.0 mL, 567.5 mmol) (2.5M in hexane) was added and the mixture was stirred for 30 minutes. 2-Chloro-4-methylpyridine (36.20 g, 283.8 mmol) in THF (100 mL) was added, and the mixture was stirred for 2 hours. A mixture of diethyl carbonate (37.82 mL, 312.1 mmol) and hexamethylphosphoramide (54.31 mL, 312.1 mmol) was added, and the mixture was stirred at −78° C. for one hour and then stirred at ambient temperature. The reaction was quenched with 25% ammonium chloride solution and extracted twice with ethyl acetate. The combined organic extracts were washed with brine, dried and evaporated. The crude oil was purified by silica gel chromatography, eluting with 5% ethyl acetate/hexane to provide the desired product as clear oil (42.75 g, 75.47% yield).

Provenance & Evidence