Ammonium Chloride → 4-(3,4-Dimethoxyphenyl)-2,2-dimethyl-4-oxobutanoic acid

HRID 1161842Notes

Reaction equation

HRID 1161842 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5](Br)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[Mg].[CH3:13][C:14]1([CH3:21])[CH2:18][C:17](=[O:19])[O:16][C:15]1=[O:20].[Cl-].[NH4+]>O1CCCC1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:17](=[O:19])[CH2:18][C:14]([CH3:21])([CH3:13])[C:15]([OH:20])=[O:16])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 76114Benzene, 4-bromo-1,2-dimethoxy-HCID 870672,2-Dimethylsuccinic anhydrideHCID 5462224Magnesium

Product 1

HCID 247272564-(3,4-Dimethoxyphenyl)-2,2-dimethyl-4-oxobutanoic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Under an atmosphere of dry nitrogen a grignard solution, prepared from 43.4 g 3,4-dimethoxybromo-benzene and 6.1 g magnesium in 200 ml of tetrahydrofuran, is added dropwise to a solution of 20.5 g 3,3-dimethyl-dihydro-furan-2,5-dione in 200 ml of tetrahydrofuran cooled in an ice-bath. The reaction mixture is stirred for an additional hour at RT. 100 ml of a 20% ammonium chloride solution is added and the water layer is extracted twice with 75 ml of ethyl acetate. The combined organic layers are washed twice with 100 ml of half saturated brine and extracted with 3×100 ml 1M sodium hydroxide solution. The aqueous layers are washed with 75 ml of ethyl acetate, acidified with concentrated hydrochloric acid and extracted 3 times with 100 ml of dichloromethane. The organic layers are dried over magnesium sulfate, filtered and concentrated in vacuo. The oily residue is crystallized from ethyl acetate/petroleum ether (60-80° C.). M. p. 114-116° C.

Workup

  1. temperaturecooled in an ice-bath
  2. extractionthe water layer is extracted twice with 75 ml of ethyl acetate
  3. washThe combined organic layers are washed twice with 100 ml of half saturated brine
  4. extractionextracted with 3×100 ml 1M sodium hydroxide solution
  5. washThe aqueous layers are washed with 75 ml of ethyl acetate
  6. extractionextracted 3 times with 100 ml of dichloromethane
  7. dry with materialThe organic layers are dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe oily residue is crystallized from ethyl acetate/petroleum ether (60-80° C.)

Sources & evidence

ORD record
ord-b38753c06a6948a6ac2437720ff336d9
Source dataset
uspto-grants-2010_10
Patent number
US07820669B2

Reaction notes

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