Hydrochloric Acid → HCID 23326050, compound

HRID 1380253Notes

Reaction equation

HRID 1380253 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)([C:10]2[CH2:11][CH2:12][N:13]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:14][CH:15]=2)O)=[CH:4][CH:3]=1.Cl.[CH3:31][OH:32]>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)=[C:10]2[CH2:11][CH2:12][N:13]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:14][CH:15]2[O:32][CH3:31])=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 887MethanolHCID 23326057HCID 23326057, compound

Product 1

HCID 23326050HCID 23326050, compoundYield 57%

Conditions

Temperature
60 °C

Procedure

A mixture of 50.9 parts of α,α-bis(4-fluorophenyl)-1,2,3,6-tetrahydro-1-(phenylmethyl)-4-pyridinemethanol, 320 parts of methanol and 800 parts of a hydrochloric acid solution 1N was stirred first for 3 hours at reflux temperature and then for 56 hours at room temperature. The whole was evaporated till all traces of methanol were removed. The free base was liberated with ammonium hydroxide. The product was extracted with 1040 parts of dichloromethane. The extract was washed with 100 parts of water, dried, filtered and evaporated. The residue was dissolved in 270 parts of N,N-dimethylformamide. The whole was heated to 60° C. 2.5 Parts of a sodium hydride dispersion 50% were added at 80° C. After stirring for 1 hour at 80° C., the mixture was cooled to room temperature. 9 Parts of iodomethane were added dropwise. Upon completion, the whole was stirred and heated for 30 minutes at 40° C. After cooling, the reaction mixture was poured onto 2000 parts of ice-water. The product was extracted twice with 450 parts of methylbenzene. The combined extracts were dried, filtered and evapoated. The oily residue was purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (98:2 by volume) as eluent. The pure fractions were collected and the eluent was evaporated, yielding 29.6 parts (57%) of 4-[bis(4-fluorophenyl)methylene]-3-methoxy-1-(phenylmethyl)piperidine as a residue (intermediate 29).

Workup

  1. temperatureat reflux temperature
  2. waitfor 56 hours at room temperature
  3. customThe whole was evaporated till all traces of methanol
  4. customwere removed
  5. extractionThe product was extracted with 1040 parts of dichloromethane
  6. washThe extract was washed with 100 parts of water
  7. customdried
  8. filtrationfiltered
  9. customevaporated
  10. dissolutionThe residue was dissolved in 270 parts of N,N-dimethylformamide
  11. addition2.5 Parts of a sodium hydride dispersion 50% were added at 80° C
  12. stirringAfter stirring for 1 hour at 80° C.
  13. temperaturethe mixture was cooled to room temperature
  14. addition9 Parts of iodomethane were added dropwise
  15. stirringUpon completion, the whole was stirred
  16. temperatureheated for 30 minutes at 40° C
  17. temperatureAfter cooling
  18. additionthe reaction mixture was poured onto 2000 parts of ice-water
  19. extractionThe product was extracted twice with 450 parts of methylbenzene
  20. customThe combined extracts were dried
  21. filtrationfiltered
  22. customThe oily residue was purified by column-chromatography over silica gel using
  23. additiona mixture of trichloromethane and methanol (98:2 by volume) as eluent
  24. customThe pure fractions were collected
  25. customthe eluent was evaporated

Sources & evidence

ORD record
ord-32beca48ce464f1fb60ddefe86ab0d00
Source dataset
uspto-grants-1986_04
Patent number
US04581171

Reaction notes

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