Phosphorus oxychloride → 4-Chloro-6-(difluoromethoxy)-2-[[(2,3-difluorophenyl)methyl]thio]-pyrimidine

HRID 1958907Notes

Reaction equation

HRID 1958907 reaction equation
[F:1][CH:2]([F:21])[O:3][C:4]1[N:9]=[C:8]([S:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[C:13]=2[F:19])[N:7]=[C:6](O)[CH:5]=1.P(Cl)(Cl)([Cl:24])=O>COCCOC.[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.O>[Cl:24][C:6]1[CH:5]=[C:4]([O:3][CH:2]([F:21])[F:1])[N:9]=[C:8]([S:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[C:13]=2[F:19])[N:7]=1

Participants

6

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 1785166036-(Difluoromethoxy)-2-[[(2,3-difluorophenyl)methyl]thio]-4-pyrimidinol2×

Product 1

HCID 866198714-Chloro-6-(difluoromethoxy)-2-[[(2,3-difluorophenyl)methyl]thio]-pyrimidine

Reagents, catalysts & solvents 3

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of 6-(difluoromethoxy)-2-[[(2,3-difluorophenyl)methyl]thio]-4-pyrimidinol (product of step i) (0.4 g) in 1,2-dimethoxyethane was added benzyltriethylammonium chloride (3 mg) and phosphorous oxychloride (0.23 mL). The resulting mixture was heated to reflux for 16 hours. The reaction mixture was cooled then diluted with H2O and extracted with EtOAc. The organic layer was washed with H2O and dried (MgSO4), filtered and evaporated. Purification was by column chromatography on silica gel using EtOAc/isohexane (2:8) as eluent to give the subtitle compound as a clear, colourless oil. Yield: 0.35 g

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureto reflux for 16 hours
  3. temperatureThe reaction mixture was cooled
  4. extractionextracted with EtOAc
  5. washThe organic layer was washed with H2O
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customevaporated
  9. customPurification

Sources & evidence

ORD record
ord-15ddc5a3e3e040d4ac9ee9024a2b3c29
Source dataset
uspto-grants-2013_04
Patent number
US08410123B2

Reaction notes

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