1-Bromo-3-fluorobenzene → 1-Benzyl-4-(3-fluorophenyl)piperidin-4-ol

HRID 2111599Notes

Reaction equation

HRID 2111599 reaction equation
[Mg].Br[C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([F:9])[CH:4]=1.[CH2:10]([N:17]1[CH2:22][CH2:21][C:20](=[O:23])[CH2:19][CH2:18]1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>C1COCC1>[CH2:10]([N:17]1[CH2:22][CH2:21][C:20]([C:3]2[CH:8]=[CH:7][CH:6]=[C:5]([F:9])[CH:4]=2)([OH:23])[CH2:19][CH2:18]1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

5

Reactant 3

HCID 140821-Bromo-3-fluorobenzeneHCID 192201-Benzyl-4-piperidoneHCID 5462224Magnesium

Product 1

HCID 221271671-Benzyl-4-(3-fluorophenyl)piperidin-4-olYield 66.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Procedure

To a suspension of 5.86 g of magnesium in 25 ml of THF is slowly added a solution of 42.16 g of 1-bromo-3-fluorobenzene in 100 ml of THF so as to reach and then maintain reflux of the THF, and the mixture is left at reflux for 1 hour with stirring. After cooling to rt, a solution of 38 g of 1-benzyl-4-piperidinone in 175 ml of THF is then added dropwise and the mixture is refluxed for 1 hour. After cooling to rt, the reaction mixture is poured into ice and extracted with EtOAc, the organic phase is washed with water and dried over Na2SO4, and the solvent is evaporated off under vacuum. 38 g of the expected product are obtained after crystallization from cyclohexane.

Workup

  1. temperaturemaintain
  2. waitthe mixture is left
  3. temperatureat reflux for 1 hour
  4. temperaturethe mixture is refluxed for 1 hour
  5. temperatureAfter cooling to rt
  6. additionthe reaction mixture is poured into ice
  7. extractionextracted with EtOAc
  8. washthe organic phase is washed with water
  9. dry with materialdried over Na2SO4
  10. customthe solvent is evaporated off under vacuum

Sources & evidence

ORD record
ord-0098ced07b3c42ed92b7f48845290390
Source dataset
uspto-grants-2009_04
Patent number
US07521449B2

Reaction notes

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