Diethyl Ether → (4-Fluorophenyl)[4-phenyl-1-(phenylmethyl)-4-piperidinyl]methanone

HRID 325918Notes

Reaction equation

HRID 325918 reaction equation
[Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][CH:4]=1.[O:10](CC)CC.Cl.[C:16]1([C:22]2([C:35]#N)[CH2:27][CH2:26][N:25]([CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH2:24][CH2:23]2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>CC1C=CC=CC=1>[F:9][C:6]1[CH:7]=[CH:8][C:3]([C:35]([C:22]2([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:27][CH2:26][N:25]([CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH2:24][CH2:23]2)=[O:10])=[CH:4][CH:5]=1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 99931-Bromo-4-fluorobenzeneHCID 5462224MagnesiumHCID 126520624-Piperidinecarbonitrile, 4-phenyl-1-(phenylmethyl)-, hydrochloride (1:1)

Product 1

HCID 15586470(4-Fluorophenyl)[4-phenyl-1-(phenylmethyl)-4-piperidinyl]methanoneYield 81%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a stirred and refluxing Grignard-complex previously prepared starting from 14.6 parts of magnesium and 105 parts of 1-bromo-4-fluorobenzene in 450 parts of 1,1'-oxybisethane, was added dropwise a solution of 94 parts of 4-phenyl-1-(phenylmethyl)-4-piperidinecarbonitrile monohyrochloride in 360 parts of methylbenzene. About 250 parts of 1,1'-oxybisethane were distilled off at an internal temperature of 60°-65° C. The turbid solution was stirred and refluxed for 5 hours. The reaction mixture was decomposed with a saturate ammonium chloride solution in water. The layers were separated and the organic phase was dried, filtered and evaporated. The oily residue was boiled in a dilute hydrochloric acid solution. After cooling, the whole was alkalized with ammonium hydroxide and extracted with trichloromethane. The extract was dried, filtered and evaporated. The residue was crystallized from a mixture of 2-propanol and 2,2'-oxybispropane, yielding 91 parts (81%) of (4-fluorophenyl)[4-phenyl-1-(phenylmethyl)-4-piperidinyl]methanone; mp. 147.6° C. (intermediate 13).

Workup

  1. temperaturerefluxing Grignard-complex
  2. custompreviously prepared
  3. distillationAbout 250 parts of 1,1'-oxybisethane were distilled off at an internal temperature of 60°-65° C
  4. stirringThe turbid solution was stirred
  5. temperaturerefluxed for 5 hours
  6. customThe layers were separated
  7. customthe organic phase was dried
  8. filtrationfiltered
  9. customevaporated
  10. temperatureAfter cooling
  11. extractionextracted with trichloromethane
  12. customThe extract was dried
  13. filtrationfiltered
  14. customevaporated
  15. customThe residue was crystallized from a mixture of 2-propanol and 2,2'-oxybispropane

Sources & evidence

ORD record
ord-0613cf2b94c1495d88ba5ee541358ced
Source dataset
uspto-grants-1984_04
Patent number
US04443451

Reaction notes

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