Acetone → 6-fluoro-2,2-dimethyl-3,4-dihydro-2H-1-benzopyran-4-one

HRID 1911261Notes

Reaction equation

HRID 1911261 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([OH:11])=[C:6]([C:8](=[O:10])[CH3:9])[CH:7]=1.[CH3:12][C:13](=O)[CH3:14].N1CCCC1.CCOC(C)=O>CO>[F:1][C:2]1[CH:7]=[C:6]2[C:5](=[CH:4][CH:3]=1)[O:11][C:13]([CH3:14])([CH3:12])[CH2:9][C:8]2=[O:10]

Participants

6

Reactant 4

HCID 180AcetoneHCID 8857Ethyl AcetateHCID 31268PyrrolidineHCID 959922-Acetyl-4-fluorophenol

Product 1

HCID 110632936-fluoro-2,2-dimethyl-3,4-dihydro-2H-1-benzopyran-4-oneYield 56.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

In a 500 mL round-bottomed flask was added 1-(5-fluoro-2-hydroxyphenyl)ethanone (20.0 g, 130 mmol, Aldrich Chemical), propan-2-one (19.0 mL, 260 mmol), and pyrrolidine (21.5 mL, 260 mmol) in methanol (150 mL) to give a orange solution. The reaction mixture was stirred at ambient temperature for 48 h. The reaction mixture was poured into EtOAc (200 mL) and washed with 1N HCl (50 mL), saturated NaHCO3 (50 mL), and brine (50 mL). The organic portion was dried (Na2SO4), filtered, and concentrated to provide an orange residue which was purified by silica gel chromatography (gradient elution, 0-20% EtOAc/hexanes) to provide the title compound (14.2 g, 73.1 mmol, 56%) as a white solid. MS (DCI/NH3) m/z 208 (M+NH4)+.

Workup

  1. customto give a orange solution
  2. washwashed with 1N HCl (50 mL), saturated NaHCO3 (50 mL), and brine (50 mL)
  3. dry with materialThe organic portion was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto provide an orange residue which
  7. customwas purified by silica gel chromatography (gradient elution, 0-20% EtOAc/hexanes)

Sources & evidence

ORD record
ord-19c5157fa79d485f998e9cf4f9ec781c
Source dataset
uspto-grants-2013_12
Patent number
US08604053B2

Reaction notes

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