Phosphorus oxychloride → 4-Chloro-6-(2,6-diethyl-phenyl)-nicotinic acid methyl ester

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Reaction Conditions

Reaction Steps

A mixture of 6-(2,6-diethyl-phenyl)-4-methoxy-nicotinic acid methyl ester (4.0 g, 13.4 mmol), DMF (10 mL) and POCl3 (10 mL) is heated at 80° C. overnight. The volatile material is removed in vacuo. Ice water, NaHCO3 and hexane (50 mL) are added to the residue. The organic layer is separated and the aqueous layer is extracted with hexane (2×30 mL). The combined organic layer is washed with water, dried, and concentrated. The crude product is purified by silica gel chromatography (1% MeOH in CH2Cl2) to give 4-chloro-6-(2,6-diethyl-phenyl)-nicotinic acid methyl ester. 1H NMR (CDCl3) 9.12 (s, 1H), 7.40 (s, 1H), 7.30 (d, 1H), 7.15 (d, 2H), 4.00 (s, 3H), 2.30 (q, 4H), 1.05 (t, 6H).

Provenance & Evidence