Chloride → 5-fluoro-2,2,7-trimethylbenzofuran-3(2H)-one

HRID 445840Notes

Reaction equation

HRID 445840 reaction equation
[F:1][C:2]1[CH:14]=[CH:13][C:5]([O:6][C:7]([CH3:12])([CH3:11])[C:8]([OH:10])=O)=[C:4]([CH3:15])[CH:3]=1.CN(C=O)C.[Cl-].[Al+3].[Cl-].[Cl-].[Cl-]>O1CCCC1>[F:1][C:2]1[CH:3]=[C:4]([CH3:15])[C:5]2[O:6][C:7]([CH3:12])([CH3:11])[C:8](=[O:10])[C:13]=2[CH:14]=1

Participants

6

Reactant 4

HCID 312ChlorideHCID 6228DimethylformamideHCID 6451240Aluminum(III) ChlorideHCID 585663572-(4-Fluoro-2-methylphenoxy)-2-methylpropanoic acid

Product 1

HCID 585662995-fluoro-2,2,7-trimethylbenzofuran-3(2H)-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-(4-fluoro-2-methylphenoxy)-2-methylpropanoic acid (658) (5 g, 23.6 mmol) in tetrahydrofuran (50 mL) at 0° C. was added cat. DMF and oxayl chloride (2.5 mL, 28.3 mmol). The reaction was warmed to room temperature, stirred for 1 hour, and concentrated in vacuo. The oil was dissolved in dichloromethane (50 mL), cooled to −78° C. and AlCl3 (7.6 g, 56.6 mmol) was added. The reaction was allowed to warm to room temperature overnight. Ice water was added and the dichloromethane was removed in vacuo. The aqueous phase was extracted with ethyl acetate (3×50 mL) and washed with saturated sodium bicarbonate dried over sodium sulfate, filtered and concentrated in vacuo. The crude compound was purified by flash column chromatography on silica gel with hexanes and EtOAc (20%) to provide 5-fluoro-2,2,7-trimethylbenzofuran-3(2H)-one (659).

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionThe oil was dissolved in dichloromethane (50 mL)
  3. temperaturecooled to −78° C.
  4. temperatureto warm to room temperature overnight
  5. customthe dichloromethane was removed in vacuo
  6. extractionThe aqueous phase was extracted with ethyl acetate (3×50 mL)
  7. washwashed with saturated sodium bicarbonate
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude compound was purified by flash column chromatography on silica gel with hexanes and EtOAc (20%)

Sources & evidence

ORD record
ord-9a1637a60f094dc396a09b99fdd8d0f4
Source dataset
uspto-grants-2013_07
Patent number
US08476308B2

Reaction notes

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