Citric Acid → 2-Benzoyl-4-(2-bromo-5-fluorophenyl)-4-methylvaleric acid-methyl ester

HRID 1247558Notes

Reaction equation

HRID 1247558 reaction equation
I([O-])(=O)(=O)=O.[Na+].[C:7]([CH:15]([C:28]1[O:29][CH:30]=CC=1)[CH2:16][C:17]([C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=1[Br:27])([CH3:19])[CH3:18])(=[O:14])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[O-:33]S([O-])=O.[Na+].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O.CI.C(=O)([O-])[O-].[Cs+].[Cs+]>O.C(#N)C.ClC(Cl)(Cl)Cl.C(#N)C.CC(OC)(C)C.O.[Ru](=O)=O>[CH3:30][O:29][C:28](=[O:33])[CH:15]([C:7](=[O:14])[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[CH2:16][C:17]([C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=1[Br:27])([CH3:18])[CH3:19]

Participants

11

Reactant 6

HCID 311Citric AcidHCID 6328Methyl iodideHCID 10796Cesium carbonateHCID 24437Sodium SulfiteHCID 219083812-[1-Benzoyl-3-(2-bromo-5-fluorophenyl)-3-methylbutyl]furanHCID 23667635Sodium periodate

Product 1

HCID 695164952-Benzoyl-4-(2-bromo-5-fluorophenyl)-4-methylvaleric acid-methyl ester

Reagents, catalysts & solvents 4

HCID 16211523Ruthenium dioxide hydrateCatalystHCID 6342AcetonitrileSolventHCID 15413tert-Butyl methyl etherSolventHCID 22592919water acetonitrile CCl4Solvent

Procedure

A suspension of 10.9 g (50.8 mmol) of sodium periodate in 140 ml of water-acetonitrile-tetrachloromethane (4:2:1) is mixed with 45 mg (0.34 mmol) of ruthenium(IV)oxide-hydrate. After 10 minutes, a solution of 2-[1-benzoyl-3-(2-bromo-5-fluorophenyl)-3-methylbutyl]furan in 40 ml of acetonitrile is added to it, it is stirred for another 10 minutes, and the batch is poured into 400 ml of saturated Na2SO3. A pH of 5 is set with 10% citric acid, and the batch is extracted with ethyl acetate. The combined extracts are dried (Na2SO4) and concentrated by evaporation in a vacuum. The residue is taken up in 8 ml of DMF and treated with 0.42 ml (6.8 mmol) of methyl iodide and 2.21 g (6.8 mmol) of cesium carbonate. After 5 hours at room temperature, the batch is diluted with 600 ml of MTBE, washed with 10% sulfuric acid and saturated NaCl, dried (Na2SO4) and concentrated by evaporation in a vacuum. Column chromatography on silica gel with hexane-ethyl acetate yields 0.9 g of product.

Workup

  1. extractionthe batch is extracted with ethyl acetate
  2. dry with materialThe combined extracts are dried (Na2SO4)
  3. concentrationconcentrated by evaporation in a vacuum
  4. waitAfter 5 hours at room temperature
  5. washwashed with 10% sulfuric acid and saturated NaCl
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated by evaporation in a vacuum

Sources & evidence

ORD record
ord-340c402c668a44dbaf76b8f63c707132
Source dataset
uspto-grants-2006_10
Patent number
US07129270B2

Reaction notes

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