Ethanol → 6-Chloro-5-methylnicotinic acid ethyl ester

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Reaction Steps

A solution of 6-chloro-5-methyl-nicotinic acid (13.85 g, 80.75 mmol) in dry ethanol (200 mL) containing some drops of concentrated H2SO4 is stirred at reflux for 2 days. The solution is cooled to rt, the solvent evaporated, the residue dissolved in EA (200 mL) and washed with a solution of sat. aq. Na2CO3 (2×80 mL), 1M aq. KHSO4 (2×80 mL) and brine (50 mL). The org. phase is dried over MgSO4, filtered and evaporated to give 6-chloro-5-methyl-nicotinic acid ethyl ester (12.65 g) as a solid; LC-MS: tR=0.92 min; [M+1]+=200.10; 1H NMR (CDCl3) δ 1.43 (t, J=7.0 Hz, 3H), 2.46 (s, 3H), 4.43 (q, J=7.3 Hz, 2H), 8.16 (m, 1H), 8.84 (d, J=2.0 Hz, 1H).

Provenance & Evidence