Piperidine → HCID 13093871, compound

Participants

Reaction Steps

The compounds of the invention of formula (I) may be prepared by the procedure described by C. A. Buehler and D. E. Pearson in "Survey of Organic Syntheses" at pages 900-901, Wiley-Interscience, New York (1970). The procedure comprises reacting 4-diphenylmethylpiperidine available from Reilly Tar and Chemical of Indianapolis, Ind. 46204, with acetic formic anhydride, the anhydride preferably being present in excess. The piperidine and anhydride are combined with cooling and are allowed to stir for about 18 hours. The resulting reaction mixture dissolved in an organic solvent such as, for example, a halocarbon e.g., carbon tetrachloride, chloroform, 1,2-dichloroethane, and the like, an aromatic hydrocarbon e.g., benzene, xylene, toluene, and the like is then treated with an aqueous solution of a weak base e.g., sodium bicarbonate, until the aqueous layer is neutral. The organic layer is separated and any solvent present is removed to obtain the intermediate N-formyl-4-(diphenylmethyl)piperidine. The N-formyl intermediate is then treated either neat or in the presence of an organic solvent such as, for example, a halocarbon, e.g., CHCl3, CH2Cl2 or a hydrocarbon e.g., benzene or toluene, at 25° to 100° C. with a suitable activating agent selected from, for example, phosgene, (CH3)3O+BF4-, (C2H5)3O+BF4-, (CH3O)2SO2, CH3OSO2F, POCl3, PCl5 and the like, for about one-half to three hours, to produce the activated formamide after which the reaction mixture is allowed to cool. Addition of the appropriate primary amine of the formula H2N--Alk--R 1 yields the desired product of formula (I) which may be isolated and purified by techniques known in the art, e.g., by stripping off the solvent and recrystallizing the desired product in the free base or acid addition salt form.

Provenance & Evidence