Sodium Carbonate → 2,4-Dichloro-6-(3-chloro-4-fluoro-phenyl)-pyrimidine

HRID 230942Notes

Reaction equation

HRID 230942 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[C:4]([Cl:9])[N:3]=1.[Cl:10][C:11]1[CH:12]=[C:13](B(O)O)[CH:14]=[CH:15][C:16]=1[F:17].C(=O)([O-])[O-].[Na+].[Na+].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.COCCOC>[Cl:1][C:2]1[N:3]=[C:4]([Cl:9])[CH:5]=[C:6]([C:13]2[CH:14]=[CH:15][C:16]([F:17])=[C:11]([Cl:10])[CH:12]=2)[N:7]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 773782,4,6-TrichloropyrimidineHCID 27346603-Chloro-4-fluorophenylboronic Acid (contains varying amounts of Anhydride)

Product 1

HCID 577610582,4-Dichloro-6-(3-chloro-4-fluoro-phenyl)-pyrimidine

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

Combine 2,4,6-trichloropyrimidine (9.15 g, 0.05 mol), 3-chloro-4-fluorophenylboronic acid (8.7 g, 0.05 mol), 1,2-dimethoxyethane (300 mL), and 2M aqueous sodium carbonate (25 mL) and let stir under nitrogen for 10 minutes. Add palladium acetate (56 mg, 0.25 mmol) and PPh3 (131 mg, 0.5 mmol) and reflux the mixture for 16 hours. Evaporate, add water (100 mL), and extract twice with DCM (25 mL each). Dry the organic layer with sodium sulfate and evaporate, giving a yellow gum. The mixture is chromatographed with 20:1 hexanes/EtOAc, affording 2,4-dichloro-6-(3-chloro-4-fluoro-phenyl)-pyrimidine as a white solid.

Workup

  1. customEvaporate
  2. additionadd water (100 mL)
  3. extractionextract twice with DCM (25 mL each)
  4. dry with materialDry the organic layer with sodium sulfate
  5. customevaporate
  6. customgiving a yellow gum
  7. customThe mixture is chromatographed with 20:1 hexanes/EtOAc

Sources & evidence

ORD record
ord-3bec91da9bee48d9bc65f4b58cff5aa6
Source dataset
uspto-grants-2009_07
Patent number
US07566712B2

Reaction notes

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