Ethyl chloroformate → HCID 53952976, compound

Participants

Reaction Steps

Triethylamine (0.47 ml) was added to a suspension of 2-methylpyridine-3-carboxylic acid (0.46 g) in dichloromethane and the mixture cooled in ice water. Ethyl chloroformate (0.33 ml) was added with stirring and the mixture allowed to warm to ambient temperature during 18 hours. (S)-4-(Aminomethyl)-1-(7-chloro-1,4-benzodioxan-2-ylmethyl)piperidine (1.0 g) was added and stirring continued for 24 hours. The solvent was evaporated and the residue triturated with water, collected by filtration, and purified by flash chromatography over silica eluting with a 3:1, then a 2:1, then a 1:1 mixture of ethyl acetate and methanol. Appropriate fractions were combined and the solvent removed in vacuo to give still impure product. Repeat flash chromatography over silica eluting with a 10:1 mixture of dichloromethane and methanol, then an 18:1:1 mixture of dichloromethane, methanol and triethylamine, followed by removal of solvent in vacuo from the appropriate fractions, gave (S)-N-{[1-(7-chloro-1,4-benzodioxan-2-ylmethyl)-4-piperidyl]methyl}-2-methylpyridine-3-carboxamide (330 mg) as a colourless solid m.p. 133-136° C. [α]D -46.6° (c=0.837, methanol).

Provenance & Evidence