Potassium Carbonate → 2-Chloro-5-fluoro-4-(4-fluoro-2-methoxyphenyl)pyrimidine

HRID 2277743Notes

Reaction equation

HRID 2277743 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([F:9])=[CH:4][N:3]=1.[F:10][C:11]1[CH:16]=[CH:15][C:14](B(O)O)=[C:13]([O:20][CH3:21])[CH:12]=1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.C(OCC)(=O)C>[Cl:1][C:2]1[N:7]=[C:6]([C:14]2[CH:15]=[CH:16][C:11]([F:10])=[CH:12][C:13]=2[O:20][CH3:21])[C:5]([F:9])=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 2507052,4-Dichloro-5-fluoropyrimidineHCID 2782672(4-Fluoro-2-methoxyphenyl)boronic acid

Product 1

HCID 867296092-Chloro-5-fluoro-4-(4-fluoro-2-methoxyphenyl)pyrimidineYield 34.2%

Reagents, catalysts & solvents 2

HCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A batch with 2,4-dichloro-5-fluoropyrimidine (200 mg; 1.20 mmol; Aldrich Chemical Company Inc.), (4-fluoro-2-methoxyphenyl)boronic acid (224 mg; 1.31 mmol; Aldrich Chemical Company Inc.) and tetrakis(triphenylphosphin)palladium(0) (138 mg; 0.12 mmol) in 1,2-dimethoxyethane (3.6 ml) and 2M solution of potassium carbonate (1.8 ml) was degassed using argon. The batch was stirred under argon for 16 hours at 90° C. After cooling the batch was diluted with ethyl acetate and washed with saturated aqueous sodium chloride solution. The organic phase was filtered using a Whatman filter and concentrated. The residue was purified by column chromatography (hexane/ethyl acetate 1:1) to give the desired product (106 mg; 0.41 mmol).

Workup

  1. temperatureAfter cooling the batch
  2. washwashed with saturated aqueous sodium chloride solution
  3. filtrationThe organic phase was filtered
  4. filtrationfilter
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography (hexane/ethyl acetate 1:1)

Sources & evidence

ORD record
ord-b840761541b449568e7c47d28bc521b7
Source dataset
uspto-grants-2015_09
Patent number
US09133171B2

Reaction notes

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