Hydrochloric Acid → 3-(4-Methoxyphenyl)-2,2-dimethylpropanoic acid

HRID 376913Notes

Reaction equation

HRID 376913 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[C:13]([OH:18])(=[O:17])[CH:14]([CH3:16])[CH3:15].CN(C)P(N(C)C)(N(C)C)=O.[CH3:30][O:31][C:32]1[CH:39]=[CH:38][C:35]([CH2:36]Cl)=[CH:34][CH:33]=1.Cl>O1CCCC1.CCCCCC>[CH3:15][C:14]([CH3:16])([CH2:36][C:35]1[CH:38]=[CH:39][C:32]([O:31][CH3:30])=[CH:33][CH:34]=1)[C:13]([OH:18])=[O:17]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 6590Isobutyric AcidHCID 7912DiisopropylamineHCID 12679HexamethylphosphoramideHCID 699934-Methyloxybenzyl chlorideHCID 178418339Butyllithium

Product 1

HCID 226408683-(4-Methoxyphenyl)-2,2-dimethylpropanoic acidYield 56.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

A cooled (-78 ° C.) solution of diisopropylamine (65 g, 642 mmol) in tetrahydrofuran (THF, 800 mL) was treated with 244 mL of 2.5M n-butyl lithium (610 mmol) in hexane. The reaction was stirred for 30 minutes at room temperature, cooled to -78° C. and treated dropwise with isobutyric acid (26.8 g, 305 mmol) and hexamethylphosphoramide (HMPA, 54.7 g, 305 mmol). The reaction was stirred for 30 minutes at room temperature and treated with 4-methoxybenzyl chloride (43.4 g, 277 mmol). The reaction was stirred for 48 hours at room temperature and treated with 10% HCl (200 mL). The reaction was concentrated to 300 mL and diluted to 600 mL with water. The resulting solution was extracted with diethyl ether (2×300 mL) and the combined ether extracts were washed with 10% HCl (2×200 mL). The ether extract was then extracted with 1N NaOH (3×200 mL). The combined 1N NaOH washes were made acidic (pH 1) by the addition of concentrated HCl, and the resulting solution was extracted with diethyl ether (3×300 mL). The combined ether extracts were dried over anhydrous magnesium sulfate, filtered, and concentrated to afford 32.6 g of 2,2-dimethyl-3-(4-methoxyphenyl)propionic acid as an oil: GC/EI-MS, m/z (rel. int.) 208 (M+, 7), 121 (100), 91 (5), 77 (6).

Workup

  1. temperaturecooled to -78° C.
  2. stirringThe reaction was stirred for 30 minutes at room temperature
  3. stirringThe reaction was stirred for 48 hours at room temperature
  4. concentrationThe reaction was concentrated to 300 mL
  5. additiondiluted to 600 mL with water
  6. extractionThe resulting solution was extracted with diethyl ether (2×300 mL)
  7. washthe combined ether extracts were washed with 10% HCl (2×200 mL)
  8. extractionThe ether extract
  9. extractionwas then extracted with 1N NaOH (3×200 mL)
  10. additionby the addition of concentrated HCl
  11. extractionthe resulting solution was extracted with diethyl ether (3×300 mL)
  12. dry with materialThe combined ether extracts were dried over anhydrous magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-920d192935d240628f35c19fb4557e90
Source dataset
uspto-grants-2000_02
Patent number
US06022894

Reaction notes

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