Water → Ethyl 4-(2-fluorophenyl)-2-(methylthio)-5-pyrimidinecarboxylate

HRID 883003Notes

Reaction equation

HRID 883003 reaction equation
[CH2:1]([O:3][C:4](=[O:19])[C:5]([C:10](=O)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[F:17])=[CH:6]N(C)C)[CH3:2].S(O)(O)(=O)=O.[NH2:25][C:26](=[NH:28])[SH:27].[CH3:29]C([O-])=O.[Na+].O>CN(C=O)C>[CH2:1]([O:3][C:4]([C:5]1[C:10]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[F:17])=[N:28][C:26]([S:27][CH3:29])=[N:25][CH:6]=1)=[O:19])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 517045Sodium AcetateHCID 54124074HCID 54124074, compoundHCID 178513471HCID 178513471, compound

Product 1

HCID 59421256Ethyl 4-(2-fluorophenyl)-2-(methylthio)-5-pyrimidinecarboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

3-Dimethylamino-2-(2-fluoro-benzoyl)-acrylic acid ethyl ester was dissolved in DMF (100 mL). To the solution was added isothiourea sulfate (18.92 g, 68.0 mmol) and NaOAc (23.24 g, 0.28 mol). The reaction mixture was heated at 80-90° C. overnight. Water was added to the cooled solution. The product was extracted with EtOAc (3×100 mL). The combined organic layers were washed with a saturated aqueous NaHCO3 solution and water, dried over Na2SO4, and concentrated. The crude product was purified by column chromatography (1 L silica, EtOAc) to give 4-(2-fluoro-phenyl)-2-methylsulfanyl-pyrimidine-5-carboxylic acid ethyl ester as a yellow oil (11.86 g, 40.6 mmol, 60% over 2 steps).

Workup

  1. extractionThe product was extracted with EtOAc (3×100 mL)
  2. washThe combined organic layers were washed with a saturated aqueous NaHCO3 solution and water
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe crude product was purified by column chromatography (1 L silica, EtOAc)

Sources & evidence

ORD record
ord-2bbe4968b9ae4561a3fb232734526467
Source dataset
uspto-grants-2012_08
Patent number
US08236815B2

Reaction notes

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