Water → 3-Benzyloxy-2-methyl-benzoic acid

HRID 253396Notes

Reaction equation

HRID 253396 reaction equation
[OH:1][C:2]1[C:3]([CH3:11])=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=[O:6].[H-].[Na+].[CH2:14](Br)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.O>O1CCCC1.CN(C)C=O>[CH2:14]([O:1][C:2]1[C:3]([CH3:11])=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=[O:6])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

7

Reactant 4

HCID 962WaterHCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 2520233-Hydroxy-2-methylbenzoic Acid

Product 1

HCID 118068023-Benzyloxy-2-methyl-benzoic acidYield 73%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-hydroxy-2-methyl-benzoic acid (55, 5.0 g, 0.033 mol) in tetrahydrofuran (100 mL) and N,N-dimethylformamide (50 mL), sodium hydride (4.4 g as 60% dispersion in mineral oil, 0.11 mol) was added slowly over 30 minutes and the reaction was stirred at 0° C. under an atmosphere of nitrogen. The reaction mixture was allowed to warm to room temperature, then stirred at room temperature for 1 hour. Benzyl bromide (9.0 mL, 0.076 mol) was added slowly into the reaction mixture, and the reaction mixture was stirred at room temperature overnight. The reaction mixture was poured into water, extracted with ethyl acetate, washed with a solution of ammonium chloride and ammonium hydroxide (4:1), brine, and dried over magnesium sulfate. After removal of solvent, the residue was purified by silica gel column chromatography eluting with ethyl acetate in hexane to provide the compound as a white solid (56, 5.8 g, 73%).

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred at room temperature for 1 hour
  3. stirringthe reaction mixture was stirred at room temperature overnight
  4. extractionextracted with ethyl acetate
  5. washwashed with a solution of ammonium chloride and ammonium hydroxide (4:1), brine
  6. dry with materialdried over magnesium sulfate
  7. customAfter removal of solvent
  8. customthe residue was purified by silica gel column chromatography
  9. washeluting with ethyl acetate in hexane

Sources & evidence

ORD record
ord-958d678244b24c5e8373a35e1ac5c4ca
Source dataset
uspto-grants-2011_01
Patent number
US07872018B2

Reaction notes

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