Hydrochloric Acid → 3-(4-methoxyphenyl)-3-methylbutanoic acid

HRID 1508460Notes

Reaction equation

HRID 1508460 reaction equation
[CH3:1][C:2]([CH3:7])=[CH:3][C:4]([OH:6])=[O:5].[C:8]1([O:14][CH3:15])[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[Cl-].[Al+3].[Cl-].[Cl-].Cl>ClCCl>[CH3:15][O:14][C:8]1[CH:13]=[CH:12][C:11]([C:2]([CH3:7])([CH3:1])[CH2:3][C:4]([OH:6])=[O:5])=[CH:10][CH:9]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 7519AnisoleHCID 109313-Methyl-2-butenoic acidHCID 6451240Aluminum(III) Chloride

Product 1

HCID 3168043-(4-methoxyphenyl)-3-methylbutanoic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In a dry flask was placed 3,3-dimethylacrylic acid (2.064 ml, 19.98 mmol). Dichloromethane (20 ml) and anisole (4.36 ml, 40.0 mmol) were added. Aluminum chloride (10.65 g, 80 mmol) was added in a single portion. After stirring at room temperature for 10 minutes, the reaction was heated to 65° C. After 2 hours, the reaction was cooled to room temperature and poured carefully onto 150 g of ice and 50 mL of concentrated HCl. The aqueous layer was extracted with CHCl3 (3×50 mL). The combined organics were extracted with water (150 mL) and saturated NaHCO3 (3×75 ml). These aqueous extracts were combined and acidified with 1N HCl. The acidified aqueous solution was extracted with 4×75 mL of Et2O. The Et2O extracts were dried over Mg2SO4, filtered, and concentrated. The residue was purified by flash chromatography on silica gel with 0 to 100% EtOAc/hexanes to afford 3-(4-methoxyphenyl)-3-methylbutanoic acid. 1H NMR (CDCl3, 500 MHz) δ 7.28 (d, J=8.8 Hz, 2H), 6.85 (d, J=8.8 Hz, 2H), 3.79 (s, 3H), 2.62 (s, 2H), 1.45 (s, 6H).

Workup

  1. customIn a dry flask was placed
  2. temperaturethe reaction was heated to 65° C
  3. waitAfter 2 hours
  4. temperaturethe reaction was cooled to room temperature
  5. extractionThe aqueous layer was extracted with CHCl3 (3×50 mL)
  6. extractionThe combined organics were extracted with water (150 mL) and saturated NaHCO3 (3×75 ml)
  7. extractionThe acidified aqueous solution was extracted with 4×75 mL of Et2O
  8. dry with materialThe Et2O extracts were dried over Mg2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by flash chromatography on silica gel with 0 to 100% EtOAc/hexanes

Sources & evidence

ORD record
ord-26fe531a4475483883c87475eac383e7
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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