Hydroxyphenylacetic acid → 4-(3-Methylbutoxy)benzeneacetic acid

HRID 1454095Notes

Reaction equation

HRID 1454095 reaction equation
[OH-].[Na+].[OH:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]([OH:13])=[O:12])=[CH:6][CH:5]=1.Br[CH2:15][CH2:16][CH:17]([CH3:19])[CH3:18]>C(O)C>[CH2:15]([O:3][C:4]1[CH:5]=[CH:6][C:7]([CH2:10][C:11]([OH:13])=[O:12])=[CH:8][CH:9]=1)[CH2:16][CH:17]([CH3:19])[CH3:18]

Participants

5

Reactant 3

HCID 127Hydroxyphenylacetic acidHCID 78911-Bromo-3-methylbutaneHCID 14798Sodium Hydroxide

Product 1

HCID 8216954-(3-Methylbutoxy)benzeneacetic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Aqueous sodium hydroxide solution (2.0 M; 32.9 mL, 65.8 mmol) was added in one portion to a stirred solution of p-hydroxyphenylacetic acid (5.00 g, 32.9 mmol) in ethanol (200 mL) at room temperature. After stirring for 15 min 1-bromo-3-methylbutane (4.97 g, 3.94 mL, 32.9 mmol) was added in one portion and the resulting solution heated at reflux for 12 h. The reaction was cooled to room temperature then evaporated to dryness. The residue was partitioned between dichloromethane (150 mL) and aqueous hydrochloric acid solution (1.0 M; 150 mL). The layers were separated and the aqueous phase was washed with dichloromethane (2×100 mL). The organic extracts were combined, dried (magnesium sulfate) and evaporated to dryness. The resulting white solid residue was used without purification in the preparation of R8782/83/1. LC/MS: 3.30 min; z/e 221, calcd (M−1) 221. 1H NMR (400 MHz: CDCl3): 7.25 (2H), 6.95 (2H), 4.05 (2H), 3.65 (2H), 1.95 (1H), 1.75 (2H), 1.05 (6H). The absolute regiochemistry of the product was unambiguously assigned using an HMBC correlation experiment.

Workup

  1. additionwas added in one portion
  2. temperaturethe resulting solution heated
  3. temperatureat reflux for 12 h
  4. customthen evaporated to dryness
  5. customThe residue was partitioned between dichloromethane (150 mL) and aqueous hydrochloric acid solution (1.0 M; 150 mL)
  6. customThe layers were separated
  7. washthe aqueous phase was washed with dichloromethane (2×100 mL)
  8. dry with materialdried (magnesium sulfate)
  9. customevaporated to dryness
  10. customThe resulting white solid residue was used without purification in the preparation of R8782/83/1
  11. custom3.30 min

Sources & evidence

ORD record
ord-2f73e4efbb7944f193b7081a115e90c7
Source dataset
uspto-grants-2009_01
Patent number
US07476759B2

Reaction notes

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