Toluene → Ethyl 2,6-dichloro-5-fluoropyridine-3-carboxylate

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Reaction Conditions

Reaction Steps

A suspension of 2,6-dichloro-5-fluoronicotinic acid (43 g, 205 mmol) in thionyl chloride (200 mL) and toluene (200 mL) was refluxed for 3 h to yield a clear solution. The solution was cooled and the solvent was evaporated under vacuum. The residue was cooled in an ice bath and cold anhydrous ethanol was added slowly. After stirring 15 min at 0° C., the solution was refluxed for 30 min under argon. The solution was cooled and the solvent was removed under vacuum. The residue was dissolved in ethyl acetate and washed subsequently by saturated NaHCO3 solution, water and brine. The organic phase was dried over MgSO4 and evaporated to yield 48.5 g (99%) of 2,6-dichloro-5-fluoro-nicotinic acid ethyl ester (65) as colorless viscous oil. 1H-NMR (DMSO-d6): δ 1.32 (t, J=7.2 Hz, 3H), 4.37 (q, J=7.2 Hz, 2H), 8.46 (d, J=8.0 Hz, 1H); EIMS m/z 238 (M).

Provenance & Evidence