N,N-Diethylaniline → 4-Chloro-5-methoxy-2-(methylsulfanyl)pyrimidine

HRID 658083Notes

Reaction equation

HRID 658083 reaction equation
[CH3:1][O:2][C:3]1[C:4](O)=[N:5][C:6]([S:9][CH3:10])=[N:7][CH:8]=1.P(Cl)(Cl)([Cl:14])=O.C(N(CC)C1C=CC=CC=1)C>C(#N)C>[Cl:14][C:4]1[C:3]([O:2][CH3:1])=[CH:8][N:7]=[C:6]([S:9][CH3:10])[N:5]=1

Participants

5

Reactant 3

HCID 7061N,N-DiethylanilineHCID 24813Phosphorus oxychlorideHCID 178493801HCID 178493801, compound

Product 1

HCID 2435114-Chloro-5-methoxy-2-(methylsulfanyl)pyrimidine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

5-Methoxy-2-methylsulfanyl-pyrimidin-4-ol (250 mg) is dissolved in acetonitrile (7 ml) and thereto are added phosphorus oxychloride (0.7 ml) and N,N-diethyl aniline (460 μl) and the mixture is heated under reflux for 5.5 hours. The reaction solution is evaporated azeotropically with toluene three times, and to the residue are added aqueous citric acid solution and chloroform, and the mixture is separated. The organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=19:1→17:3) to give 4-chloro-5-methoxy-2-methylsulfanyl-pyrimidine (260 mg). MS (m/z): 191/193 [M+H]+

Workup

  1. temperaturethe mixture is heated
  2. temperatureunder reflux for 5.5 hours
  3. customThe reaction solution is evaporated azeotropically with toluene three times
  4. additionto the residue are added aqueous citric acid solution and chloroform
  5. customthe mixture is separated
  6. washThe organic layer is washed with a saturated brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=19:1→17:3)

Sources & evidence

ORD record
ord-277f5048c1074e8584a00adab101b807
Source dataset
uspto-grants-2011_12
Patent number
US08076364B2

Reaction notes

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