Ethyl Acetate → Methyl 2-[[(dimethylamino)carbothioyl]oxy]-4-fluorobenzoate

HRID 499429Notes

Reaction equation

HRID 499429 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([OH:12])[C:5](=[CH:10][CH:11]=1)[C:6]([O:8][CH3:9])=[O:7].[CH3:13][N:14]([CH3:18])[C:15](Cl)=[S:16].N12CCN(CC1)CC2.C(OCC)(=O)C>CN(C=O)C.O>[CH3:13][N:14]([CH3:18])[C:15]([O:12][C:4]1[CH:3]=[C:2]([F:1])[CH:11]=[CH:10][C:5]=1[C:6]([O:8][CH3:9])=[O:7])=[S:16]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 9237DabcoHCID 27871Dimethylthiocarbamoyl chlorideHCID 2775386Methyl 4-fluorosalicylate

Product 1

HCID 59750140Methyl 2-[[(dimethylamino)carbothioyl]oxy]-4-fluorobenzoateYield 81.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

4-Fluorosalicylic acid (10.0 g, 64 mmol) was dissolved in methanol (300 ml), and concentrated sulfuric acid (6.3 g, 64 mmol) was added thereto. The reaction mixture was refluxed for 48 hrs. The solvent was evaporated, and the residue was neutralized with 2 N aqueous sodium hydroxide solution. Ethyl acetate was added to the mixture. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated to give methyl 4-fluorosalicylate (10.0 g, 92%) as white crystals. Methyl 4-fluorosalicylate (10.0 g, 58 mmol) and N,N-dimethylthiocarbamoyl chloride (9.6 g, 77 mmol) were dissolved in DMF (100 ml), and 1,4-diazabicyclo[2.2.2]octane (8.5 g, 75 mmol) was added thereto. The reaction mixture was stirred at room temperature for 7 hrs. The reaction mixture was combined with ethyl acetate and water. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated. The residue was subjected to a silica gel column chromatography. The fractions eluted with ethyl acetate-hexane (1:5, v/v) were collected, concentrated and recrystallized from ethyl acetate-hexane to give the titled compound (12.1 g, 80%) as white crystals.

Workup

  1. washThe organic layer was washed with saturated brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. customThe solvent was evaporated
  4. washThe fractions eluted with ethyl acetate-hexane (1:5
  5. customv/v) were collected
  6. concentrationconcentrated
  7. customrecrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-9af002a9c13a42b1986a40a8fc443857
Source dataset
uspto-grants-2010_08
Patent number
US07767665B2

Reaction notes

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