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

HRID 1726871Notes

Reaction equation

HRID 1726871 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-dimethoxybromobenzene 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 1 M 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 1 M 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-12b7950e88d1471ca3bc37340dbceccf
Source dataset
uspto-grants-2009_02
Patent number
US07494990B2

Reaction notes

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