Oxalic Acid → HCID 86594304, compound

Temperature

98 °C

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.

1. additionis added to this solution over 3 hours at 98-100° C.
2. temperatureto cool to 55° C.
3. customthe organic phase is separated out
4. washwashed with water
5. extractionBy 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
6. customare obtained
7. custompreheated to 85° C.
8. stirringwith stirring
9. temperatureThe mixture is heated for 12 hours at 85° C.
10. temperatureto cool to room temperature
11. filtrationThe mixture is filtered
12. concentrationconcentrated under vacuum down to about 6.5 l, 6.5 l of 4-methyl-2-pentanone
13. additionare then added
14. additionthe pH of the mixture is brought to 14 by addition of 30% sodium hydroxide
15. customThe aqueous phase is separated out
16. extractionre-extracted with 4-methyl-2-pentanone
17. customthe combined organic phases are dried via azeotropic distillation
18. customThe solution thus obtained
19. customthe precipitate thus obtained
20. filtrationis filtered off
21. washwashed with ethanol
22. customdried under vacuum at 70° C

ORD record

ord-e726c7ed8a5a484a89312a0b5f48cf83

Source dataset

uspto-grants-2005_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06916929B2