Cesium carbonate → 4-Chloro-6-ethenyl-5-fluoropyrimidine

HRID 1051192Notes

Reaction equation

HRID 1051192 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[C:6](Cl)[N:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O.[CH3:17][CH:18]1CCCO1>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[C:7]([F:8])=[C:6]([CH:17]=[CH2:18])[N:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 112866754,6-Dichloro-5-fluoropyrimidineHCID 67831299Water methyl tetrahydrofuran

Product 1

HCID 736728834-Chloro-6-ethenyl-5-fluoropyrimidineYield 71%

Reagents, catalysts & solvents 2

HCID 11776TriphenylphosphineCatalystHCID 178418476HCID 178418476, compoundCatalyst

Procedure

4,6-Dichloro-5-fluoropyrimidine (6 g, 36.0 mmol) was reacted with potassium vinyl trifluoroborate (1.60 g, 37.8 mmol, 1.05 eq), and caesium carbonate (17.58 g, 1.5 eq) in water/methyl tetrahydrofuran. The reaction was treated with Pd(PPh3)2Cl2 (504 mg, 0.02 eq) and PPh3 (189 mg, 0.02 eq) under argon. The reaction was heated to reflux and held under reflux for 20 hours. The reaction was quenched by the addition of further water and tert-butyl methyl ether. The organic phase was atmospherically distilled to remove the solvents. The residue was purified by column chromatography, 12-100% dichloromethane in hexane. The combined fractions were concentrated by fractional distillation to give 4.1 g (71% yield) of the product as a slightly yellow oil.

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux
  3. temperatureunder reflux for 20 hours
  4. customThe reaction was quenched by the addition of further water and tert-butyl methyl ether
  5. distillationThe organic phase was atmospherically distilled
  6. customto remove the solvents
  7. customThe residue was purified by column chromatography, 12-100% dichloromethane in hexane
  8. concentrationThe combined fractions were concentrated by fractional distillation

Sources & evidence

ORD record
ord-d70bcc73846f49feaf4cc92f814be32f
Source dataset
uspto-grants-2016_07
Patent number
US09388167B2

Reaction notes

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