Benzyl Bromide → 2-Benzyloxy-6-methoxybenzoic Acid Benzyl Ester

HRID 554542

Reaction equation

HRID 554542 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]([OH:12])[C:8]=1[C:9]([OH:11])=[O:10].[H-].[Na+].[CH2:15](Br)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[Cl-].[NH4+]>O.CN(C=O)C>[CH2:15]([O:10][C:9](=[O:11])[C:8]1[C:3]([O:2][CH3:1])=[CH:4][CH:5]=[CH:6][C:7]=1[O:12][CH2:9][C:8]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

7

Reactant 4

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 5915242-Hydroxy-6-methoxybenzoic acid

Product 1

HCID 674612312-Benzyloxy-6-methoxybenzoic Acid Benzyl EsterYield 118.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

While stirring a mixture of 6-methoxysalicylic acid (5.07 g, 30.15 mmol) and sodium hydride (60% w/w, 3.02 g, 75.38 mmol) under cooling with ice, DMF (30 mL) was added thereto. The mixture solution was stirred at the same temperature for 10 minutes, and then benzyl bromide (8.95 mL, 75.38 mmol) was added thereto over 5 minutes and the reaction mixture was stirred at the same temperature for 30 minutes and at room temperature for 2.5 hours. To the reaction mixture was added a saturated ammonium chloride aqueous solution and water under cooling with ice, and the mixture was extracted with ether. The organic layer was washed with water and a saturated ammonium chloride aqueous solution and dried (anhydrous sodium sulfate), and then the solvent was distilled under reduce pressure. The obtained residue was purified by silica gel column chromatography [developing solution=ethyl acetate:n-hexane (1:10 to 1:5)] to obtain the title compound (6.24 g, 59%).

Workup

  1. additionwas added
  2. stirringThe mixture solution was stirred at the same temperature for 10 minutes
  3. stirringthe reaction mixture was stirred at the same temperature for 30 minutes and at room temperature for 2.5 hours
  4. temperatureunder cooling with ice
  5. extractionthe mixture was extracted with ether
  6. washThe organic layer was washed with water
  7. dry with materiala saturated ammonium chloride aqueous solution and dried (anhydrous sodium sulfate)
  8. distillationthe solvent was distilled
  9. customThe obtained residue was purified by silica gel column chromatography [developing solution=ethyl acetate:n-hexane (1:10 to 1:5)]

Sources & evidence

ORD record
ord-b529aa7dabe94287b9e915ab20f82d76
Source dataset
uspto-grants-2011_11
Patent number
US08048897B2

Linked notes

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