Acetic Anhydride → N-(1-(5-Fluoropyrimidin-2-yl)vinyl)acetamide

HRID 75951Notes

Reaction equation

HRID 75951 reaction equation
[F:1][C:2]1[CH:3]=[N:4][C:5]([C:8]#[N:9])=[N:6][CH:7]=1.C[Mg+].[Br-].[C:13](OC(=O)C)(=[O:15])[CH3:14].[C:20](=O)(O)[O-].[Na+]>C1COCC1.CCOCC.C(Cl)Cl>[F:1][C:2]1[CH:3]=[N:4][C:5]([C:8]([NH:9][C:13](=[O:15])[CH3:14])=[CH2:20])=[N:6][CH:7]=1

Participants

8

Reactant 4

HCID 7918Acetic AnhydrideHCID 516892Sodium BicarbonateHCID 441818675-Fluoropyrimidine-2-carbonitrileHCID 178418689HCID 178418689, compound

Product 1

HCID 45119272N-(1-(5-Fluoropyrimidin-2-yl)vinyl)acetamideYield 26%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

5-Fluoropyrimidine-2-carbonitrile (Method 59, 1.0 g, 8.1 mmol) in THF (10 ml) was added a solution of MeMgBr (3.3 ml, 9.75 mmol) in ether drop wise at 0° C. After addition, the reaction was warmed to room temperature, stirred at room temperature for 1 hour and then diluted with DCM (10 ml). Acetic anhydride (1.23 ml, 13.0 mmol) was added in one portion. The reaction was stirred at room temperature for 1 hour and 40° C. for 1 hour. Saturated sodium bicarbonate solution (10 ml) was added and extracted with EtOAc (2×20 ml). The combined organic was dried over sodium sulfate. After removal of solvent, the resulted residue was purified by column chromatography (hexane-EtOAc=2.5:1) to give the title compound as a white solid (0.38 g, 26%). 1H NMR (400 MHz) 9.34 (s, 1H), 8.95 (s, 2H), 6.25 (s, 1H), 6.03 (s, 1H), 2.11 (s, 3H). MS: Calcd.: 181. Found: [M+H]+ 182.

Workup

  1. customdrop wise at 0° C
  2. additionAfter addition
  3. stirringThe reaction was stirred at room temperature for 1 hour and 40° C. for 1 hour
  4. extractionextracted with EtOAc (2×20 ml)
  5. dry with materialThe combined organic was dried over sodium sulfate
  6. customAfter removal of solvent
  7. customthe resulted residue was purified by column chromatography (hexane-EtOAc=2.5:1)

Sources & evidence

ORD record
ord-d4985df5af034b53a3f2c6cc72b09dfe
Source dataset
uspto-grants-2014_09
Patent number
US08835465B2

Reaction notes

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