Benzene → 3-Benzoylpiperidine hydrochloride

HRID 1703400Notes

Reaction equation

HRID 1703400 reaction equation
S(Cl)([Cl:3])=O.C([N:8]1[CH2:16][CH2:15][CH2:14][CH:10]([C:11]([OH:13])=O)[CH2:9]1)(=O)C.[Cl-].[Al+3].[Cl-].[Cl-].[CH:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>>[ClH:3].[C:11]([CH:10]1[CH2:14][CH2:15][CH2:16][NH:8][CH2:9]1)(=[O:13])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

5

Reactant 4

HCID 241BenzeneHCID 24386Thionyl ChlorideHCID 6451240Aluminum(III) ChlorideHCID 140438961-Acetyl-3-piperidinecarboxylic acid

Product 1

HCID 197720583-Benzoylpiperidine hydrochlorideYield 16%

Conditions

Temperature
60 °C

Procedure

The method is that of U.S. Pat. No. 3,576,810. To 500 ml. of thionyl chloride was added 85.6 g. (0.5 mole) of 1-acetylnipecotic acid. The stirred mixture was heated at ca. 60° C. for two hours and then the solvent was evaporated at reduced pressure. The crude acid chloride was taken up in 200 ml. of dry benzene and the resulting solution added slowly to a mixture of 133 g. (1.0 mole) of aluminum chloride in 400 ml. of dry benzene. After the addition was complete the mixture was refluxed one hour and then poured onto cracked ice. The organic layer was separated and the aqueous layer was extracted with benzene. The combined extracts were dried over magnesium sulfate and the solvent was evaporated at reduced pressure. The residual oil which did not crystallize on cooling was distilled at reduced pressure and the fraction boiling at 160°-170° C./0.05 mm. collected. The crude product weighed 50 g. A mixture of 50 g. of the crude 1 -acetyl-3-benzoylpyrrolidine and 200 ml. of 6 N hydrochloric acid was refluxed 12 hours, cooled and extracted with benzene. The combined extracts were washed with water, dried over magnesium sulfate and the solvent evaporated at reduced pressure. The residual oil weighed 15.1 g. (16% yield). A portion (2.5 g.) of the free base was dissolved in 50 ml. of isopropanol and treated with ethereal hydrogen chloride. The white crystalline salt which formed weighed 2.4 g. and melted at 193°-195° C.

Workup

  1. customthe solvent was evaporated at reduced pressure
  2. additionof dry benzene and the resulting solution added slowly to a mixture of 133 g
  3. additionAfter the addition
  4. temperaturewas refluxed one hour
  5. additionpoured
  6. customThe organic layer was separated
  7. extractionthe aqueous layer was extracted with benzene
  8. dry with materialThe combined extracts were dried over magnesium sulfate
  9. customthe solvent was evaporated at reduced pressure
  10. customThe residual oil which did not crystallize
  11. temperatureon cooling
  12. distillationwas distilled at reduced pressure
  13. customcollected
  14. additionA mixture of 50 g
  15. temperatureof 6 N hydrochloric acid was refluxed 12 hours
  16. temperaturecooled
  17. extractionextracted with benzene
  18. washThe combined extracts were washed with water
  19. dry with materialdried over magnesium sulfate
  20. customthe solvent evaporated at reduced pressure
  21. dissolutionA portion (2.5 g.) of the free base was dissolved in 50 ml
  22. additionof isopropanol and treated with ethereal hydrogen chloride
  23. customThe white crystalline salt which formed

Sources & evidence

ORD record
ord-5f7f39e7e76d4a588d770f85ca7e3fa6
Source dataset
uspto-grants-1982_09
Patent number
US04351940

Reaction notes

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