Acetone → 2,2-Dimethyl-7-(trifluoromethyl)chroman-4-one

HRID 1911270Notes

Reaction equation

HRID 1911270 reaction equation
[OH:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[C:12](=[O:14])[CH3:13].[CH3:15][C:16]([CH3:18])=O.N1CCCC1>CO>[CH3:15][C:16]1([CH3:18])[CH2:13][C:12](=[O:14])[C:3]2[C:2](=[CH:7][C:6]([C:8]([F:9])([F:10])[F:11])=[CH:5][CH:4]=2)[O:1]1

Participants

5

Reactant 3

HCID 180AcetoneHCID 31268PyrrolidineHCID 154464491-[2-Hydroxy-4-(trifluoromethyl)phenyl]ethan-1-one

Product 1

HCID 582559392,2-Dimethyl-7-(trifluoromethyl)chroman-4-oneYield 75.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The crude 1-[2-hydroxy-4-(trifluoromethyl)phenyl]ethanone (9.90 g, 48.5 mmol) from above was dissolved in methanol (100 mL) and acetone (3.56 mL, 48.5 mmol), and pyrrolidine (8.02 mL, 97.0 mmol) were added. The reaction was stirred at ambient temperature for 14 h; LCMS showed reaction completion. The reaction mixture was concentrated and diluted with EtOAc (300 mL), then washed with water (100 mL), 2N HCl (2×100 mL), water (50 mL), 2N NaOH (2×100 mL), water (50 mL), and brine (20 mL). The organic portion was dried (Na2SO4), filtered, concentrated, and the residue purified by silica gel chromatography (gradient elution, 0-20% EtOAc/hexanes) to give the title compound (8.93 g, 36.6 mmol, 75%) as a white solid. MS (ESI) m/z 245 (M+H)+.

Workup

  1. customreaction completion
  2. concentrationThe reaction mixture was concentrated
  3. additiondiluted with EtOAc (300 mL)
  4. washwashed with water (100 mL), 2N HCl (2×100 mL), water (50 mL), 2N NaOH (2×100 mL), water (50 mL), and brine (20 mL)
  5. dry with materialThe organic portion was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customthe residue purified by silica gel chromatography (gradient elution, 0-20% EtOAc/hexanes)

Sources & evidence

ORD record
ord-b7444b0afbcb4e869b7a4175d49b0c6a
Source dataset
uspto-grants-2013_12
Patent number
US08604053B2

Reaction notes

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