Potassium Carbonate → 1-[2,4-Bis(trifluoromethyl)benzyl]piperidine-4-carbaldehyde

HRID 1620471Notes

Reaction equation

HRID 1620471 reaction equation
Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([F:12])([F:11])[F:10])=[CH:5][C:4]=1[C:13]([F:16])([F:15])[F:14].[NH:17]1[CH2:22][CH2:21][CH:20]([CH2:23][OH:24])[CH2:19][CH2:18]1.C(=O)([O-])[O-].[K+].[K+].O.C(OCC)(=O)C>CN(C)C=O>[F:14][C:13]([F:16])([F:15])[C:4]1[CH:5]=[C:6]([C:9]([F:12])([F:11])[F:10])[CH:7]=[CH:8][C:3]=1[CH2:2][N:17]1[CH2:22][CH2:21][CH:20]([CH:23]=[O:24])[CH2:19][CH2:18]1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 4207714-PiperidinemethanolHCID 5188712,4-Bis(trifluoromethyl)benzyl bromideHCID 22728543Water ethylacetate

Product 1

HCID 866786631-[2,4-Bis(trifluoromethyl)benzyl]piperidine-4-carbaldehydeYield 86.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(bromomethyl)-2,4-bis(trifluoromethyl)benzene (89 g) in N,N-dimethylformamide (1 L) were added 4-piperidinemethanol (50 g) and potassium carbonate (60.0 g), and the mixture was stirred at room temperature for 2 hr. Water/ethyl acetate were added to the reaction mixture, and the organic layer was separated, washed with water and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. To a solution of the obtained oil and triethylamine (242 mL) in dimethyl sulfoxide (1 L) was added sulfur trioxide pyridine complex (138 g), and the mixture was stirred at room temperature for 1 hr. Water/ethyl acetate were added to the reaction mixture, and the organic layer was separated, washed with water and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (85 g).

Workup

  1. customthe organic layer was separated
  2. washwashed with water and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. additionTo a solution of the obtained oil and triethylamine (242 mL) in dimethyl sulfoxide (1 L) was added sulfur trioxide pyridine complex (138 g)
  6. stirringthe mixture was stirred at room temperature for 1 hr
  7. additionWater/ethyl acetate were added to the reaction mixture
  8. customthe organic layer was separated
  9. washwashed with water and saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customthe solvent was evaporated under reduced pressure
  12. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-a436f1852f9840fd8fa5badf2dce8976
Source dataset
uspto-grants-2014_07
Patent number
US08772277B2

Reaction notes

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