Oxalyl chloride → 2-Chloronicotinoyl chloride

A mixture of 2-chloronicotinic acid (2-chloro-3-pyridylcarboxylic acid, 4.0 g, 25.4 mmol), oxalyl chloride (2.28 ml, 26.65 mmol) and two drops of DMF are stirred in chloroform (60 ml) for 30 minutes and subsequently refluxed for 45 minutes. The volatiles are distilled under reduced pressure to give crude 2-chloronicotinoyl chloride. This crude product is added to a mixture of diethyl malonate (3.85 ml, 25.38 mmol), magnesium chloride (2.4 g, 25.38 mmol) and triethylamine (7 ml, 50.77 mmol) in acetonitrile (25 ml) with cooling, such that the temperature does not rise above 15° C. After stirring for 24 hours the reaction mixture is diluted with ether and washed repeatedly with 1 M hydrochloric acid and brine. Drying of the organic phase over magnesium sulfate, filtering and evaporation of the solvents gives crude diethyl 2-(2-chloronicotinoyl)-malonate. This crude product is dissolved in DMSO (40 ml) and water (3 ml), and is heated at 140-150° C. for four hours. The mixture is poured onto crushed ice and the product is extracted using ether. Filtering of the ether phase over a pad of silicagel gives 3-acetyl-2-chloropyridine as a yellow oil; 1H-NMR (CDCl3, 300 MHz): 8.50 (dd, 1H); 7.91 (dd, 1H); 7.34 (ddd, 1H); 2.71 (s, 3H).

1. temperaturesubsequently refluxed for 45 minutes
2. distillationThe volatiles are distilled under reduced pressure

ORD record

ord-72d006c3bac94cbc8c2a08badb6648e6

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08486996B2