Sodium Bicarbonate → 4-[5-carbomethoxymethyl-1H-indol-3-yl]N-methylpiperidine

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Reaction Steps

A solution of 1-methyl-4 (formylmethyl)piperidine (2.3 g, 16 mmol) and 4-(ethoxycarbonylmethyl)phenyl hydrazine hydrochloride (3.7 g, 16 mmol) in methanol:water (20:1) (25 ml) was stirred at room temperature for 1 hour. Polyphosphoric acid (7 g) was then added and the mixture heated at reflux for 5 hours, under nitrogen. The mixture was then cooled to ambient temperature, basified with saturated sodium bicarbonate to pH9, and extracted with dichloromethane (2×20 ml). The organic phases were combined, dried (MgSO4) and evaporated to give a brown residue. This was chromatographed (eluant 50:8:1 dichloromethane:ethanol:ammonia) to give 4-[5-carbomethoxymethyl-1H-indol-3-yl]N-methylpiperidine (1.8 g, 39%) as a yellow solid. mp 105°-107° C. δ(360 MHz, CDCl3) δ1.85 (2H, m), 2.16 (4H, m), 2.36 (3H, s), 2.81 (1H, m), 3.00 (2H, m), 3.70 (3H, s), 3.73 (2H, s), 6.97 (1H, d, J=2 Hz), 7.10 (1H, dd, J=8 and Hz), 7.31 (1H, d, J=8 Hz), 7.53 (1H, s), 7.97 (1H, brs).

Provenance & Evidence