Benzyl Bromide → Methyl 3-(benzyloxy)-5-hydroxybenzoate

HRID 883042Notes

Reaction equation

HRID 883042 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[C:8]([OH:10])[CH:7]=[C:6]([OH:11])[CH:5]=1.C(=O)([O-])[O-].[K+].[K+].C1OCCOCCOCCOCCOCCOC1.[CH2:37](Br)[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>CC(C)=O>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:5]=[C:6]([OH:11])[CH:7]=[C:8]([O:10][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH:9]=1

Participants

6

Reactant 4

HCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 2855718-Crown-6HCID 75076Methyl 3,5-Dihydroxybenzoate

Product 1

HCID 7472028Methyl 3-(benzyloxy)-5-hydroxybenzoateYield 26%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

1.1 3, 5-Dihydroxy-benzoic acid methyl ester (149 mmol), potassium carbonate (1 eq.) and 18-crown-6 (0.1 eq.) are dissolved in acetone (750 ml) and stirred for 1 hour at RT. Benzylbromide (0.8 eq.) is added and the reaction solution is heated to reflux for 8 hours. The solvent is removed in vacuo and 3-benzyloxy-5-hydroxy-benzoic acid methyl ester is isolated after column chromatography in a yield of 26%. The isolated compound is dissolved in acetone (180 ml), potassium carbonate (1.2 eq.) and isopropyl iodide (2. eq.) is added and the reaction solution is heated under reflux for 24 hours. The reaction is quenched with water and extracted with ethyl acetate. The combined organic layer is dried over Na2SO4 and the solvent removed in vacuo. 3-Benzyloxy-5-isopropoxy-benzoic acid methyl ester is obtained after column chromatography in a yield of 67%. The isolated compound is dissolved in methanol/TNF/water (90 ml, 1:1:1) and LiOH (4 eq.) is added. The reaction is stirred for 2 hours at RT and quenched with citric acid solution and the pH was adjusted to 7. The solution is extracted with ethyl acetate and the combined organic layers are dried over Na2SO4 and the solvent is removed in vacuo. 3-Benzyloxy-5-isopropoxy-benzoic acid is isolated as a brown powder in a yield of 93%; HPLC (Method 8): 3.43 min; LC-MS (Method B): 2.391 min, 287.15 (M+H+);

Workup

  1. temperaturethe reaction solution is heated
  2. temperatureto reflux for 8 hours
  3. customThe solvent is removed in vacuo

Sources & evidence

ORD record
ord-8ded571d20924796bbdc3baf6121a858
Source dataset
uspto-grants-2012_08
Patent number
US08236824B2

Reaction notes

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