Hydrochloric Acid → 1-(2-Chloro-5-fluoropyrimidin-4-yl)ethanone

HRID 470192Notes

Reaction equation

HRID 470192 reaction equation
[F:1][C:2]1[C:3](Cl)=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[CH2:10]([O:12]C([Sn](C)(C)C)=C)[CH3:11].Cl>CN(C)C=O.O.[Cl-].[Na+].O.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>[Cl:8][C:5]1[N:4]=[C:3]([C:10](=[O:12])[CH3:11])[C:2]([F:1])=[CH:7][N:6]=1

Participants

8

Reactant 3

HCID 313Hydrochloric AcidHCID 2507052,4-Dichloro-5-fluoropyrimidineHCID 11096550(1-Ethoxyethenyl)(trimethyl)stannane

Product 1

HCID 865947381-(2-Chloro-5-fluoropyrimidin-4-yl)ethanoneYield 92%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 5-fluoro-2,4-dichloro-pyrimidine (20 g, 119.8 mmol) and (1-ethoxyethenyl)trimethylstannane (43.26 g, 119.8 mmol) in dimethylformamide (200 mL) is purged at room temperature with nitrogen and bis(triphenylphosphine)palladium(II) chloride (1.70 g, 2.40 mmol) is then added. The resulting mixture is heated at 70° C. for 2 hours under nitrogen. The reaction is cooled to 50° C. and aqueous 5 N hydrogen chloride (100 mL) is added. The reaction is stirred at 50° C. for two more hours. The reaction is cooled, diluted with water (200 mL) and brine. This solution is extracted five times with diethyl ether. The combined organic layers are dried over sodium sulfate and concentrated under vacuum. The crude product is purified over silica gel with a 30 minute, 5% to 50% ethyl acetate in hexanes gradient, to give the title compound (19.2 g, 92%). GC/MS (m/e): (35Cl/37Cl) 174/176.

Workup

  1. additionis then added
  2. temperatureThe reaction is cooled to 50° C.
  3. temperatureThe reaction is cooled
  4. extractionThis solution is extracted five times with diethyl ether
  5. dry with materialThe combined organic layers are dried over sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customThe crude product is purified over silica gel with a 30 minute

Sources & evidence

ORD record
ord-777c9b21ed3e425b984bd7b9c880cbf4
Source dataset
uspto-grants-2014_01
Patent number
US08629270B2

Reaction notes

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