Benzyl Bromide → Methyl 5-(benzyloxy)-2-hydroxybenzoate

HRID 1746454Notes

Reaction equation

HRID 1746454 reaction equation
C([O-])([O-])=O.[K+].[K+].[OH:7][C:8]1[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][C:9]=1[C:10]([O:12][CH3:13])=[O:11].Br[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>CO.C(Cl)(Cl)Cl.CO.C(Cl)(Cl)Cl>[CH2:20]([O:18][C:15]1[CH:16]=[CH:17][C:8]([OH:7])=[C:9]([CH:14]=1)[C:10]([O:12][CH3:13])=[O:11])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

7

Reactant 3

HCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 75077Methyl Gentisate

Product 1

HCID 13026913Methyl 5-(benzyloxy)-2-hydroxybenzoateYield 69%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6212ChloroformSolventHCID 21584188Chloroform methanolSolvent

Procedure

To a refluxed suspension of K2CO3 (32.8 g, 238 mmol) in methanol (180 mL) and CHCl3 (350 mL) was then added a mixture of methyl 2,5-dihydroxybenzoate (10.0 g, 59.5 mmol) and bromomethylbenzene (7.10 mL, 59.5 mmol) in methanol/CHCl3 (50 mL/25 mL) drop wise over 30 minutes. The resulting mixture was stirred at reflux for another 4 hours. After cooling down and filtration, the filter cake was washed with CHCl3 (20 mL). The combined filtrate was concentrated under reduced pressure. The residue was redissolved in CHCl3 (200 mL), washed with HCl (1N) (100 mL×2). The organic was then washed with brine (100 mL), dried over Na2SO4, filtered, and concentrated. The residue was purified by silica gel column chromatography eluting with petroleum ether/EtOAc (8:1) to give methyl 5-(benzyloxy)-2-hydroxybenzoate (10.6 g, 69.0%) as a white solid.

Workup

  1. additionwas then added
  2. temperatureat reflux for another 4 hours
  3. temperatureAfter cooling down
  4. filtrationfiltration
  5. washthe filter cake was washed with CHCl3 (20 mL)
  6. concentrationThe combined filtrate was concentrated under reduced pressure
  7. dissolutionThe residue was redissolved in CHCl3 (200 mL)
  8. washwashed with HCl (1N) (100 mL×2)
  9. washThe organic was then washed with brine (100 mL)
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe residue was purified by silica gel column chromatography
  14. washeluting with petroleum ether/EtOAc (8:1)

Sources & evidence

ORD record
ord-6e0ee51bbfe24313acb2052bee8589bd
Source dataset
uspto-grants-2015_10
Patent number
US09150526B2

Reaction notes

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