Ethyl Acetate → (2-Methoxy-4-methylsulfanyl-phenyl)-methanol

HRID 982860Notes

Reaction equation

HRID 982860 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[C:10]([S:12][CH3:13])[CH:9]=[CH:8][C:4]=1[C:5](O)=[O:6].C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>C1COCC1.O>[CH3:1][O:2][C:3]1[CH:11]=[C:10]([S:12][CH3:13])[CH:9]=[CH:8][C:4]=1[CH2:5][OH:6]

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 6433294-(Methylthio)-o-anisic acid

Product 1

HCID 22562107(2-Methoxy-4-methylsulfanyl-phenyl)-methanolYield 51%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

2-Methoxy-4-methylsulfanyl-benzoic acid (2 g, 10.09 mmol) was dissolved in dry THF (20 mL) and the solution was stirred while heated to 60° C. under nitrogen and then borane-methylsulfide complex (1.7 eq, 1.7 mL, 17.5 mmol) was added very slowly dropwise via a syringe. The progress of the reaction was followed by both TLC and analytical HPLC and when complete (3 hours) the mixture was allowed to cool to room temperature, diluted with water (10 mL) added extremely slowly dropwise under nitrogen. Potassium carbonate (1 g) was added and after stirring the mixture for 30 minutes ethyl acetate (50 ml) was added. The organic layer was separated, washed with water, 2 N hydrochloric acid, water and brine, dried over Na2SO4 and then concentrated to a near colorless oil. The residue was triturated with hexane and product was purified from the resulting crystals by flash column chromatography to provide (2-methoxy-4-methylsulfanyl-phenyl)-methanol (934 mg, 51%) as colorless crystals. LCMS: M−182.8.

Workup

  1. additionborane-methylsulfide complex (1.7 eq, 1.7 mL, 17.5 mmol) was added very slowly dropwise via a syringe
  2. customwas followed by both TLC and analytical HPLC and when complete (3 hours)
  3. temperatureto cool to room temperature
  4. additionadded extremely slowly dropwise under nitrogen
  5. additionwas added
  6. customThe organic layer was separated
  7. washwashed with water, 2 N hydrochloric acid, water and brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated to a near colorless oil
  10. customThe residue was triturated with hexane and product
  11. customwas purified from the resulting crystals by flash column chromatography

Sources & evidence

ORD record
ord-86763ed0b1c1488fa8600f4511347b5f
Source dataset
uspto-grants-2005_03
Patent number
US06861419B2

Reaction notes

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