Citric Acid → 4-(2-Bromo-5-fluorophenyl)-2-hydroxy-4-methylvaleric acid-methyl ester

HRID 1836180Notes

Reaction equation

HRID 1836180 reaction equation
[CH3:1][O:2][C:3](=[O:25])[CH:4](C(=O)C1C=CC=CC=1)[CH2:5][C:6]([C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[Br:16])([CH3:8])[CH3:7].C(=O)([O-])[O-:27].[K+].[K+].S(=O)(=O)(O)O.C(=O)([O-])[O-].[Cs+].[Cs+].CI.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CO>[CH3:1][O:2][C:3](=[O:25])[CH:4]([OH:27])[CH2:5][C:6]([C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[Br:16])([CH3:8])[CH3:7]

Participants

8

Reactant 6

HCID 311Citric AcidHCID 1118Sulfuric AcidHCID 6328Methyl iodideHCID 10796Cesium carbonateHCID 11430Potassium CarbonateHCID 695164952-Benzoyl-4-(2-bromo-5-fluorophenyl)-4-methylvaleric acid-methyl ester

Product 1

HCID 695167344-(2-Bromo-5-fluorophenyl)-2-hydroxy-4-methylvaleric acid-methyl esterYield 36.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 0.9 g (2.13 mmol) of 2-benzoyl-4-(2-bromo-5-fluorophenyl)-4-methylvaleric acid-methyl ester in 50 ml of MeOH is mixed with 1.47 g (10.6 mmol) of potassium carbonate and stirred for 3 hours at room temperature. The batch is acidified (pH 3) with 10% sulfuric acid, and it is extracted with ethyl acetate. The combined extracts are washed with saturated NaCl, dried (Na2SO4) and concentrated by evaporation in a vacuum. The residue is taken up in 8 ml of DMF and stirred with 1.92 g (5.9 mmol) of cesium carbonate and 0.38 ml (5.9 mmol) of methyl iodide for 3 hours at room temperature. The batch is mixed with 10% citric acid and extracted with MTBE. The organic phase is washed with saturated NaCl, dried (Na2SO4) and concentrated by evaporation in a vacuum. Column chromatography on silica gel with hexane-ethyl acetate yields 250 mg of product.

Workup

  1. extractionis extracted with ethyl acetate
  2. washThe combined extracts are washed with saturated NaCl
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated by evaporation in a vacuum
  5. extractionextracted with MTBE
  6. washThe organic phase is washed with saturated NaCl
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated by evaporation in a vacuum

Sources & evidence

ORD record
ord-30b911221be14f81b9604f042370b16e
Source dataset
uspto-grants-2004_08
Patent number
US06777409B2

Reaction notes

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