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

HRID 536449Notes

Reaction equation

HRID 536449 reaction equation
[CH3:1][C:2]([CH3:4])=O.N1CCCC1.[OH:10][C:11]1[CH:16]=[C:15]([C:17]([F:20])([F:19])[F:18])[CH:14]=[CH:13][C:12]=1[C:21](=[O:23])[CH3:22]>CO>[CH3:1][C:2]1([CH3:4])[CH2:22][C:21](=[O:23])[C:12]2[C:11](=[CH:16][C:15]([C:17]([F:18])([F:19])[F:20])=[CH:14][CH:13]=2)[O:10]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%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Acetone (3.56 mL, 48.5 mmol) and pyrrolidine (8.02 mL, 97.0 mmol) were added to a solution of Example 3A in methanol (100 mL). The reaction mixture was stirred at ambient temperature for 14 hours concentrated, 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 layer was dried (Na2SO4), filtered, and concentrated. The residue was 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. concentrationconcentrated
  2. additiondiluted with EtOAc (300 mL)
  3. 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)
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography (gradient elution, 0-20% EtOAc/hexanes)

Sources & evidence

ORD record
ord-f4139d27d80a499ca5f9bb580676dc5c
Source dataset
uspto-grants-2014_10
Patent number
US08859584B2

Reaction notes

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