Ethyl bromoacetate → 2-Methoxy-6-isopropylphenoxyacetic Acid

HRID 967012Notes

Reaction equation

HRID 967012 reaction equation
Br[CH2:2][C:3]([O:5]CC)=[O:4].[OH-].[Na+].[CH:10]([C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[C:14]=1[OH:21])([CH3:12])[CH3:11]>C1(C)C=CC=CC=1.[Cl-].C([N+](CC)(CC)CC1C=CC=CC=1)C.O>[CH3:20][O:19][C:15]1[CH:16]=[CH:17][CH:18]=[C:13]([CH:10]([CH3:12])[CH3:11])[C:14]=1[O:21][CH2:2][C:3]([OH:5])=[O:4]

Participants

7

Reactant 3

HCID 7748Ethyl bromoacetate2×HCID 14798Sodium HydroxideHCID 125212842-Methoxy-6-(propan-2-yl)phenol

Product 1

HCID 105133162-Methoxy-6-isopropylphenoxyacetic AcidYield 72%

Reagents, catalysts & solvents 3

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolvent3×

Procedure

A solution of 11.1 ml of ethyl bromoacetate in 10 ml of toluene was added dropwise at room temperature over about 15 minutes into a mixture of 20 g of NaOH, 30 ml of H2O, 1.1 g of triethylbenzylammonium chloride, 8.4 g of 2-isopropyl-6-methoxyphenol (prepared according to Johnson et al., Tetrahedron. 38, 1397-1404 (1982)) and 40 ml of toluene. The mixture was stirred vigorously at the same temperature for 2 h and thereafter for 2 h at 60-65° C. and for 6.5 h under reflux. During this last step a solution of 6 ml of ethyl bromoacetate in 10 ml of toluene was added. In the end the mixture was diluted with 250 ml of H2O. The aqueous phase was separated off and treated with concentrated HCl; the emulsified precipitate was extracted with Et2O (3×50 ml) and the organic phase was washed with water. Another extraction was performed with 40 ml of 20% Na2CO3 and the slightly alkaline solution was treated with concentrated HCl and extracted with Et2O (3×40 ml). The extracts were pooled and the solvent was evaporated off, giving 8 g (72%) of the desired compound; b.p. 190° C./0.7 mmHg.

Workup

  1. waitfor 2 h at 60-65° C.
  2. temperaturefor 6.5 h under reflux
  3. customThe aqueous phase was separated off
  4. additiontreated with concentrated HCl
  5. extractionthe emulsified precipitate was extracted with Et2O (3×50 ml)
  6. washthe organic phase was washed with water
  7. extractionAnother extraction
  8. additionthe slightly alkaline solution was treated with concentrated HCl
  9. extractionextracted with Et2O (3×40 ml)
  10. customthe solvent was evaporated off

Sources & evidence

ORD record
ord-960af535151542ae9883fe7adefa1fe0
Source dataset
uspto-grants-2005_10
Patent number
US06953800B2

Reaction notes

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