Piperidine → HCID 13093871, compound

HRID 1981911Notes

Reaction equation

HRID 1981911 reaction equation
[C:1]1([CH:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:20](OC(=O)C)=[O:21].N1CCCCC1.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.C1(C)C(C)=CC=CC=1.C1C=CC=CC=1.ClCCCl.C(Cl)(Cl)Cl.C(Cl)(Cl)(Cl)Cl>[CH:20]([N:11]1[CH2:10][CH2:9][CH:8]([CH:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:13][CH2:12]1)=[O:21]

Participants

11

Reactant 4

HCID 8082PiperidineHCID 75269Acetic-formic anhydrideHCID 882784-BenzhydrylpiperidineHCID 516892Sodium Bicarbonate

Product 1

HCID 13093871HCID 13093871, compound

Reagents, catalysts & solvents 6

HCID 111,2-DichloroethaneSolventHCID 241BenzeneSolventHCID 1140TolueneSolventHCID 5943Carbon TetrachlorideSolventHCID 6212ChloroformSolventHCID 7237O-XyleneSolvent

Procedure

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.

Workup

  1. temperaturewith cooling
  2. customThe resulting reaction mixture
  3. dissolutiondissolved in an organic solvent such as, for example
  4. customThe organic layer is separated
  5. customany solvent present is removed

Sources & evidence

ORD record
ord-f990e8c84da241da95b9f56bc0ff8d7b
Source dataset
uspto-grants-1986_06
Patent number
US04594351

Reaction notes

Loading…