Salicylic Acid → Methyl 2-(benzyloxy)benzoate

HRID 2185971Notes

Reaction equation

HRID 2185971 reaction equation
[C:1]([OH:10])(=[O:9])[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4].O=S(Cl)Cl.[CH:15]1[CH:20]=[CH:19][C:18]([CH2:21]Br)=[CH:17][CH:16]=1.[C:23]([O-])([O-])=O.[K+].[K+]>CO.CCOC(C)=O.[Na+].[I-]>[CH2:21]([O:4][C:3]1[CH:5]=[CH:6][CH:7]=[CH:8][C:2]=1[C:1]([O:10][CH3:23])=[O:9])[C:18]1[CH:19]=[CH:20][CH:15]=[CH:16][CH:17]=1

Participants

8

Reactant 4

HCID 338Salicylic AcidHCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 24386Thionyl Chloride

Product 1

HCID 251331Methyl 2-(benzyloxy)benzoateYield 60%

Reagents, catalysts & solvents 3

HCID 5238Sodium IodideCatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of salicylic acid (7 g, 0.05 mol) in methanol (100 mL) at −78° C., SOCl2 (8 mL, 0.11 mol, 2.2 equiv.) was added dropwise. The reaction mixture was stirred at 40° C. overnight, concentrated and extracted with EtOAc. The organic layer was washed with NaHCO3, brine, dried over Na2SO4, filtered and concentrated. The product was then dissolved in DMF; BnBr (9 mL, 0.075 mol, 1.5 equiv.), K2CO3(27.5 g, 0.2 mol, 4 equiv.) and NaI (75 mg) were added. The reaction mixture was stirred at room temperature for 12 h, diluted with EtOAc, washed with water, 0.5N HCl, and brine, dried over Na2SO4, filtered, concentrated and chromatographed on silica gel eluting with hexanes/EtOAc (10:1), to give methyl 2-(benzyloxy)benzoate as an oil (6.8 g, 0.03 mol, 57%). To the methyl ester was added KOH (3.2 g, 0.06 mol, 2 equiv.) and THF/H2O (1:1) (20 mL). The reaction mixture was stirred at room temperature overnight and extracted with EtOAc. The aqueous layer was acidified to pH 2 with 2N HCl and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated to afford 2-(benzyloxy)benzoic acid as white crystals (m=4.5 g, 70%).

Workup

  1. concentrationconcentrated
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed with NaHCO3, brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe product was then dissolved in DMF
  8. stirringThe reaction mixture was stirred at room temperature for 12 h
  9. washwashed with water, 0.5N HCl, and brine
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customchromatographed on silica gel eluting with hexanes/EtOAc (10:1)

Sources & evidence

ORD record
ord-48cff7d0c14042dbae1bd879edfb8443
Source dataset
uspto-grants-2002_06
Patent number
US06403623B1

Reaction notes

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