Benzene, 1-bromo-2-(trifluoromethyl)- → 1-Benzyl-4-[2-(trifluoromethyl)phenyl]piperidin-4-ol

HRID 2376640Notes

Reaction equation

HRID 2376640 reaction equation
[Mg].Br[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]([F:12])([F:11])[F:10].[CH2:13]([N:20]1[CH2:25][CH2:24][C:23](=[O:26])[CH2:22][CH2:21]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[Cl-].[NH4+]>C1COCC1>[CH2:13]([N:20]1[CH2:25][CH2:24][C:23]([C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[C:9]([F:12])([F:11])[F:10])([OH:26])[CH2:22][CH2:21]1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

6

Reactant 4

HCID 9806Benzene, 1-bromo-2-(trifluoromethyl)-HCID 192201-Benzyl-4-piperidoneHCID 25517Ammonium ChlorideHCID 5462224Magnesium

Product 1

HCID 232942051-Benzyl-4-[2-(trifluoromethyl)phenyl]piperidin-4-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A mixture of 1.52 g of magnesium in 25 ml of THF is admixed dropwise over 20 minutes with a solution of 14.25 g of 1-bromo-2-(trifluoromethyl)benzene in 15 ml of THF and the mixture is heated at reflux for 30 minutes. After it has cooled on an ice bath, it is admixed slowly with a solution of 10 g of 1-benzyl-4-piperidinone in 30 ml of THF and left with stirring at AT for 3 hours. The reaction mixture is poured into saturated aqueous ammonium chloride solution and extracted with AcOEt, the combined organic phases are washed with water and dried over Na2SO4 and the solvents are evaporated under vacuum. The residue is chromatographed on silica gel, eluting with a DCM/AcOEt (70/30; v/v) mixture. This gives 4.5 g of the expected product.

Workup

  1. temperaturethe mixture is heated
  2. temperatureat reflux for 30 minutes
  3. temperatureAfter it has cooled on an ice bath
  4. waitleft
  5. extractionextracted with AcOEt
  6. washthe combined organic phases are washed with water
  7. dry with materialdried over Na2SO4
  8. customthe solvents are evaporated under vacuum
  9. customThe residue is chromatographed on silica gel
  10. washeluting with a DCM/AcOEt (70/30; v/v) mixture

Sources & evidence

ORD record
ord-9b0125952ae840448a25baa3e5768c0e
Source dataset
uspto-grants-2008_12
Patent number
US07468368B2

Reaction notes

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