Tetrahydrofuran → HCID 23326078, compound

HRID 484718Notes

Reaction equation

HRID 484718 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][CH:3]=1.[Mg].O1CCCC1.[C:15]([N:18]1[CH2:23][CH2:22][CH:21]([C:24](=[O:32])[C:25]2[CH:30]=[CH:29][C:28]([Br:31])=[CH:27][CH:26]=2)[CH2:20][CH2:19]1)(=[O:17])[CH3:16]>CC1C=CC=CC=1.C(O)(=O)C>[C:15]([N:18]1[CH2:19][CH2:20][CH:21]([C:24]([C:25]2[CH:26]=[CH:27][C:28]([Br:31])=[CH:29][CH:30]=2)([C:2]2[CH:7]=[CH:6][C:5]([F:8])=[CH:4][CH:3]=2)[OH:32])[CH2:22][CH2:23]1)(=[O:17])[CH3:16]

Participants

7

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 99931-Bromo-4-fluorobenzeneHCID 5462224MagnesiumHCID 13363395HCID 13363395, compound

Product 1

HCID 23326078HCID 23326078, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 1140TolueneSolvent

Procedure

To a stirred and refluxing Grignard-complex previously prepared starting from 52.5 parts of 1-bromo-4-fluorobenzene, 7.5 parts of magnesium and 216 parts of tetrahydrofuran was added dropwise a solution of 94 parts of 1-acetyl-4-(4-bromobenzoyl)piperidine in 450 parts of tetrahydrofuran. Upon completion, stirring was continued for 5 hours at reflux. The reaction mixture was cooled, poured onto a mixture of 300 parts of crushed ice and 40 parts of acetic acid and stirred for 15 minutes. 450 Parts of methylbenzene were added. The organic layer was separated, dried, filtered and evaporated. The residue was taken up in methylbenzene and the whole was evaporated. The residue was purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (90:10 by volume) as eluent. The pure fractions were collected and the eluent was evaporated, yielding 75 parts of 1-acetyl-α-(4-bromophenyl)-α-(4-fluorophenyl)-4-piperidinemethanol as a residue (intermediate 16).

Workup

  1. temperaturerefluxing Grignard-complex
  2. custompreviously prepared
  3. stirringUpon completion, stirring
  4. temperatureat reflux
  5. temperatureThe reaction mixture was cooled
  6. stirringstirred for 15 minutes
  7. customThe organic layer was separated
  8. customdried
  9. filtrationfiltered
  10. customevaporated
  11. customthe whole was evaporated
  12. customThe residue was purified by column-chromatography over silica gel using
  13. additiona mixture of trichloromethane and methanol (90:10 by volume) as eluent
  14. customThe pure fractions were collected
  15. customthe eluent was evaporated

Sources & evidence

ORD record
ord-10fab1bb4c984801948cf81ba37bdcb9
Source dataset
uspto-grants-1985_08
Patent number
US04533665

Reaction notes

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