4-Piperidinol, 1-methyl- → Oxalate

Participants

Reaction Steps

A mixture of 2-(hydroxypyridin-2-ylmethyl)phenol (0.27 g), 4-hydroxy-1-methylpiperidine (0.31 g) and para-toluenesulfonic acid, monohydrate (0.89 g) in toluene (20 mL) and 1-methyl-2-pyrrolidinone (1 mL) is heated for 3 hours in a Dean-Stark apparatus. The mixture is cooled back to room temperature, treated with aqueous NaHCO3 and extracted twice with ethyl acetate. Pooled organic extracts are washed with brine, dried over magnesium sulfate and concentrated. The residue is purified by column chromatography over silica gel (gradient dichloromethane/methanol/ammonia from 100/0/0.5 to 95/5/0.5) to afford the pure base that is then converted into its oxalate salt in acetone to give 2-[(1-methylpiperidin-4-yloxy)pyridin-2-ylmethyl]phenol, oxalate as a solid melting at 70° C.

Provenance & Evidence