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

HRID 521699Notes

Reaction equation

HRID 521699 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 room temperature 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 with nitrogen. Bis(triphenylphosphine)palladium(II) chloride (1.70 g, 2.40 mmol) is added and the resulting mixture is heated to 70° C. for 2 hours under nitrogen. The reaction is cooled to 50° C. and aqueous 5 N hydrogen chloride (100 mL) is added and stirred for 2 hours. The reaction is cooled and diluted with water (200 mL) and brine and extracted five times with diethyl ether. The combined organic layers are dried over sodium sulfate and concentrated under vacuum. The crude product is purified using silica gel column chromatography using a 5-50% gradient of ethyl acetate in hexanes to give the title compound (19.2 g, 92%). GC/MS (m/e): 174 and 176.

Workup

  1. temperatureThe reaction is cooled to 50° C.
  2. temperatureThe reaction is cooled
  3. extractionextracted five times with diethyl ether
  4. dry with materialThe combined organic layers are dried over sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customThe crude product is purified

Sources & evidence

ORD record
ord-d08517898d074d928cc15d29891a183b
Source dataset
uspto-grants-2016_05
Patent number
US09328124B2

Reaction notes

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