Hexane → 1-Benzyl-4-(3,4-dimethoxyphenyl)piperidin-4-ol

HRID 1272277Notes

Reaction equation

HRID 1272277 reaction equation
C([Li])CCC.CCCCCC.Br[C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([O:21][CH3:22])[CH:14]=1.[CH2:23]([N:30]1[CH2:35][CH2:34][C:33](=[O:36])[CH2:32][CH2:31]1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C1COCC1.O>[CH2:23]([N:30]1[CH2:35][CH2:34][C:33]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([O:21][CH3:22])[CH:14]=2)([OH:36])[CH2:32][CH2:31]1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

7

Reactant 4

HCID 8058HexaneHCID 192201-Benzyl-4-piperidoneHCID 76114Benzene, 4-bromo-1,2-dimethoxy-HCID 178418339Butyllithium

Product 1

HCID 135355651-Benzyl-4-(3,4-dimethoxyphenyl)piperidin-4-olYield 71%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of n-butyllithium in hexane (1.56 M, 93.0 mL, 145 mmol) was added dropwise a solution of 4-bromo-1,2-dimethoxybenzene (34.4 g, 158 mmol) in THF (350 ml) under −70° C. and stirred for 30 minutes under argon atmosphere. A solution of 1-benzyl piperidin-4-one (25.0 g, 132 mmol) in THF (50 ml) was added dropwise to the reaction mixture under −60° C., and the mixture was allowed to warm to 0° C. and stirred under ice cooling for 30 minutes. The reaction mixture was diluted with water, concentrated under reduced pressure, and extracted with ethyl acetate. The organic extract was washed with water and saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified using silica gel column chromatography and the obtained crystals were washed with hexane to obtain 26.6 g (yield 71%) of the title compound. mp. 112–114° C.

Workup

  1. stirringstirred under ice cooling for 30 minutes
  2. concentrationconcentrated under reduced pressure
  3. extractionextracted with ethyl acetate
  4. extractionThe organic extract
  5. washwas washed with water and saturated aqueous sodium chloride
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified
  9. washthe obtained crystals were washed with hexane

Sources & evidence

ORD record
ord-a784dea104e5474d870d832e022c9a72
Source dataset
uspto-grants-2007_04
Patent number
US07208495B2

Reaction notes

Loading…