Ethanol → Ethyl 4-chloropyridine-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

A suspension of 4-chloro-pyridine-3-carboxylic acid (5.0 g, 31.7 mmol) in thionyl chloride (100 ml) is heated at 80° C. for 1.5 h. The reaction mixture is cooled to RT and excess thionyl chloride is distilled off. The crude product is azeotropped with toluene (3×30 ml) to afford a solid, which is added in portions to a mixture of ethanol (40 ml) and diisopropylethylamine (25 ml) at 0° C. The resulting reaction mixture is stirred at RT for 4 h. After completion of the reaction, the mixture is evaporated to dryness; the residue is diluted with water (20 ml) and extracted with EtOAc (3×25 ml). The combined organic layers are washed with water (30 ml), brine (30 ml), dried over anhydrous sodium sulfate and evaporated to get 4-chloro-pyridine-3-carboxylic acid ethyl ester (4.50 g, 24.3 mmol, 77%), which is used in the next step without further purification.

Provenance & Evidence