Potassium Hydroxide → 1-(2-Chloro-5-fluoropyrimidin-4-yl)ethanone

HRID 879637Notes

Reaction equation

HRID 879637 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8]([O:10]CC)=[CH2:9])[C:5]([F:13])=[CH:4][N:3]=1.[OH-].[K+]>Cl>[Cl:1][C:2]1[N:7]=[C:6]([C:8](=[O:10])[CH3:9])[C:5]([F:13])=[CH:4][N:3]=1

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 497880412-Chloro-4-(1-ethoxyvinyl)-5-fluoropyrimidine

Product 1

HCID 865947381-(2-Chloro-5-fluoropyrimidin-4-yl)ethanone

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

A mixture of 2-chloro-4-(1-ethoxyvinyl)-5-fluoropyrimidine (5.23 g, 25.81 mmol) in 3N HCl (100 mL) was stirred at rt for 6 h. Potassium hydroxide (50%) was added to give a cloudy mixture (pH was still less than 1) and extracted cloudy mixture with EtOAc. More potassium hydroxide (50%) was added and extracted with EtOAc. Again, more potassium hydroxide (50%) was added until pH=7 and extracted with EtOAc. The combined organic layer dried (MgSO4), filtered, concentrated and purified by CombiFlash (0 to 25% EtOAc/Hex) to give the desired product. 1H NMR (400 MHz, CDCl3) δ 8.69 (d, J=2 Hz, 1H), 2.71 (2, 3H); 19F (376 MHz, CDCl3) δ −138.26.

Workup

  1. customto give a cloudy mixture (pH
  2. extractionextracted cloudy mixture with EtOAc
  3. additionMore potassium hydroxide (50%) was added
  4. extractionextracted with EtOAc
  5. additionAgain, more potassium hydroxide (50%) was added until pH=7
  6. extractionextracted with EtOAc
  7. dry with materialThe combined organic layer dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. custompurified by CombiFlash (0 to 25% EtOAc/Hex)

Sources & evidence

ORD record
ord-0084ea9678304c868dd659d1968396cf
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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