Isopropyl iodide → Methyl 3-hydroxy-5-isopropoxybenzoate

HRID 1430982Notes

Reaction equation

HRID 1430982 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([OH:12])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].C([O-])([O-])=O.[K+].[K+].I[CH:20]([CH3:22])[CH3:21]>CC(C)=O>[CH3:8][O:7][C:5](=[O:6])[C:4]1[CH:3]=[C:2]([O:1][CH:20]([CH3:22])[CH3:21])[CH:11]=[C:10]([OH:12])[CH:9]=1

Participants

5

Reactant 3

HCID 6362Isopropyl iodideHCID 11430Potassium CarbonateHCID 75076Methyl 3,5-Dihydroxybenzoate

Product 1

HCID 23072925Methyl 3-hydroxy-5-isopropoxybenzoateYield 44.4%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a stirred solution of methyl 3,5-dihydroxybenzoate (20.0 g, 119 mmol) in acetone (500 mL) was added K2CO3 (19.7 g, 143 mmol) and 2-iodopropane (13.1 mL, 131 mmol) at rt. The resulting mixture was refluxed for 12 hr. Then the mixture was filtered through a pad of Celite to remove insoluble salts and the cake was rinsed with acetone. Combined filtrates were concentrated under vacuum to afford a residue which was purified by silica gel flash chromatography (7.5×30 cm, hexane/EtOAc, v/v 10:1, 5:1). Fractions containing the mono-alkylation product were pooled and concentrated to give 3-hydroxy-5-isopropoxy-benzoic acid methyl ester (11.1 g, 44%) as a white solid. 1H NMR (300 MHz, CDCl3): δ 7.11-7.14 (m, 2H), 6.60 (m, 1H), 4.56 (m, 1H), 3.89 (s, 3H), 1.32 (d, J=6 Hz, 6H).

Workup

  1. temperatureThe resulting mixture was refluxed for 12 hr
  2. filtrationThen the mixture was filtered through a pad of Celite
  3. customto remove insoluble salts
  4. washthe cake was rinsed with acetone
  5. concentrationCombined filtrates were concentrated under vacuum
  6. customto afford a residue which
  7. customwas purified by silica gel flash chromatography (7.5×30 cm, hexane/EtOAc, v/v 10:1, 5:1)
  8. additionFractions containing the mono-alkylation product
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-61ccb05b456a44d7a24f3eb56a22dee1
Source dataset
uspto-grants-2015_01
Patent number
US08940927B2

Reaction notes

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