Oxalic Acid → HCID 86594304, compound

Participants

Reaction Conditions

Reaction Steps

2.89 l of toluene are added to a solution of 5.54 kg of Vitride® at 70% in toluene, and the mixture is heated to 98° C. A solution, heated to 80° C., of 2.86 kg of 1-benzyl-4-methoxycarbonylamino-4-phenylpiperidine, obtained in step (a) in 1.3 l of toluene, is added to this solution over 3 hours at 98-100° C. with stirring. 3.92 l of a 5% sodium hydroxide solution are then added at 80° C. The mixture is allowed to cool to 55° C. and the organic phase is separated out by settling at this temperature and washed with water. By extracting the toluene phase with 823 g of formic acid in 8.64 l of water, 11.77 kg of a solution of 1-benzyl-4-methylamino-4-phenylpiperidine formate at pH 5.5 are obtained, and this solution is added to a mixture of 155.2 g of 5% Pd/BaSO4 and 1.35 l of demineralized water preheated to 85° C., with stirring. 96.2 g of 5% of Pd/BaSO4 and 417.4 g of formic acid are gradually added, still at 85° C. The mixture is heated for 12 hours at 85° C. and then allowed to cool to room temperature and 898.5 g of 95% sulfuric acid are added. The mixture is filtered and concentrated under vacuum down to about 6.5 l, 6.5 l of 4-methyl-2-pentanone are then added and the pH of the mixture is brought to 14 by addition of 30% sodium hydroxide. The aqueous phase is separated out by settling of the phases and re-extracted with 4-methyl-2-pentanone, and the combined organic phases are dried via azeotropic distillation. The solution thus obtained is poured into a solution of 1.57 kg of oxalic acid in 13.3 l of absolute ethanol and the precipitate thus obtained is filtered off, washed with ethanol and dried under vacuum at 70° C. 2.77 kg of 4-methylamino-4-phenylpiperidine dioxalate are thus obtained; m.p.=214-215° C. Overall yield calculated from the starting 1-benzyl-4-cyano-4-phenylpiperidine hydrochloride: 78.5% of the theoretical amount.

Provenance & Evidence