4-Methoxybenzylamine → 5-Chloro-2-(4-methoxy-benzylamino)-nicotinic Acid Methyl Ester

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Reaction Steps

A solution of 2,5-dichloro-nicotinic acid methyl ester (71) (25 g, 121 mmol) in anhydrous methanol was purged with argon and added p-methoxybenzylamine (34.5 mL, 266 mmol) at room temperature. The solution was refluxed overnight under argon. The solution was cooled and the solvent was evaporated under reduced pressure. The residue was taken in dichloromethane, sonicated briefly and undissolved solids were filtered off. The filtrate washed by water, dried over MgSO4 and concentrated. The crude product was purified by flash chromatography eluting with hexane:CH2Cl2 (1:1) to yield 16.2 g (44%) of 5-chloro-2-(4-methoxy-benzylamino)-nicotinic acid methyl ester (72) as a white solids. Mp 94° C. 1H-NMR (DMSO-d6): δ 3.71 (s, 3H), 3.82 (s, 3H), 4.59 (d, J=5.6 Hz, 2H), 6.87 (m, 2H), 7.24 (m, 2H), 8.06 (d, J=2.8 Hz, 1H), 8.27 (m, 1H), 8.32 (d, J=2.8 Hz, 1H); EIMS m/z 307 (M+1).

Provenance & Evidence