Malonic Acid → [4-Phenyl-1-(3,3,3-triphenylpropyl)piperidin-4-yl]methanol--hydrogen chloride (1/1)

HRID 616203Notes

Reaction equation

HRID 616203 reaction equation
C1(C(C2C=CC=CC=2)(C2C=CC=CC=2)O)C=CC=CC=1.C(O)(=O)CC(O)=O.[C:28]1([C:34]([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH2:35][C:36]([Cl:38])=O)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.[C:51]1([C:57]2([C:63]([O:65]CC)=O)[CH2:62][CH2:61][NH:60][CH2:59][CH2:58]2)[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+]>C(O)C.C1C=CC=CC=1.CCOCC.Cl.CC(C)=O.C(N(CC)CC)C>[ClH:38].[C:28]1([C:34]([C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=2)([C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)[CH2:35][CH2:36][N:60]2[CH2:59][CH2:58][C:57]([C:51]3[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=3)([CH2:63][OH:65])[CH2:62][CH2:61]2)[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1

Participants

13

Reactant 6

HCID 867Malonic AcidHCID 6457TriphenylcarbinolHCID 14798Sodium HydroxideHCID 32414NormeperidineHCID 15254181HCID 15254181, compoundHCID 21226445Aluminium lithium hydride2×

Product 1

HCID 20370855[4-Phenyl-1-(3,3,3-triphenylpropyl)piperidin-4-yl]methanol--hydrogen chloride (1/1)

Reagents, catalysts & solvents 6

HCID 180AcetoneSolventHCID 241BenzeneSolventHCID 313Hydrochloric AcidSolventHCID 702EthanolSolventHCID 3283Diethyl EtherSolventHCID 8471TriethylamineSolvent

Procedure

A mixture of 2 parts of triphenylcarbinol and 8 parts of malonic acid are heated at 170° for 31 hours. This mixture is cooled and then dissolved in hot ethanol. 3,3,3-Triphenylpropionic acid, melting at 182°, crystallizes from the ethanol upon cooling. 1 Part of 3,3,3-triphenylpropionic acid is then refluxed with 5 parts of thionyl chloride for 4 hours and the excess thionyl chloride is removed in vacuum to provide the crude 3,3,3-triphenylpropionyl chloride. 9 Parts of this 3,3,3-triphenylpropionyl chloride are then reacted with 27.0 parts of ethyl 4-phenyl-4-piperidinecarboxylate in the presence of 4 parts of triethylamine in benzene. The resulting amide is reduced with 5 parts of lithium aluminum hydride in ether at reflux for 2.5 hours. The reaction mixture is cooled and treated with 15% aqueous sodium hydroxide solution to decompose any unreacted lithium aluminum hydride. The reaction mixture is then filtered and washed with ether. The ether solution is evaporated to give an oil. This oil is then slurried in 10% HCl and extracted with ether. The aqueous phase which contains an insoluble oil is extracted with methylene chloride, and the methylene chloride extract dried over anhydrous sodium sulfate. Evaporation of this methylene chloride solution gives a solid which is taken up in acetone and precipitated with ether to give 1-(3,3,3-triphenylpropyl)-4-(phenyl)-4-piperidinemethanol hydrochloride, melting at about 256°-259° C.

Workup

  1. temperatureare heated at 170° for 31 hours
  2. temperatureThis mixture is cooled
  3. custom3,3,3-Triphenylpropionic acid, melting at 182°, crystallizes from the ethanol
  4. temperatureupon cooling
  5. temperature1 Part of 3,3,3-triphenylpropionic acid is then refluxed with 5 parts of thionyl chloride for 4 hours
  6. customthe excess thionyl chloride is removed in vacuum
  7. customto provide the crude 3,3,3-triphenylpropionyl chloride
  8. temperatureat reflux for 2.5 hours
  9. temperatureThe reaction mixture is cooled
  10. filtrationThe reaction mixture is then filtered
  11. washwashed with ether
  12. customThe ether solution is evaporated
  13. customto give an oil
  14. extractionextracted with ether
  15. extractionis extracted with methylene chloride
  16. extractionthe methylene chloride extract
  17. dry with materialdried over anhydrous sodium sulfate
  18. customEvaporation of this methylene chloride solution
  19. customgives a solid which
  20. customprecipitated with ether

Sources & evidence

ORD record
ord-5fee91ad873f4603aa64bd96954bec0f
Source dataset
uspto-grants-1978_02
Patent number
US04072686

Reaction notes

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