Acetic Anhydride → N-[1-(5-Fluoropyridin-2-yl)ethenyl]acetamide

HRID 450354Notes

Reaction equation

HRID 450354 reaction equation
C[Mg+].[Br-].[F:4][C:5]1[CH:6]=[CH:7][C:8]([C:11]#[N:12])=[N:9][CH:10]=1.[C:13](OC(=O)C)(=[O:15])[CH3:14].[C:20](=O)(O)[O-].[Na+]>CCOCC.C1COCC1.ClCCl>[F:4][C:5]1[CH:6]=[CH:7][C:8]([C:11]([NH:12][C:13](=[O:15])[CH3:14])=[CH2:20])=[N:9][CH:10]=1

Participants

8

Reactant 4

HCID 7918Acetic AnhydrideHCID 516892Sodium BicarbonateHCID 113324532-Cyano-5-fluoropyridine2×HCID 178418689HCID 178418689, compound

Product 1

HCID 66736029N-[1-(5-Fluoropyridin-2-yl)ethenyl]acetamideYield 35%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of MeMgBr (170.3 ml, 510.98 mmol) in ether was diluted with 170 ml of anhydrous THF and cooled to 0° C. 5-fluoropyridine-2-carbonitrile (Intermediate 1, 53.6 g, 425.82 mmol) in THF (170 ml) was added dropwise. The reaction was stirred at 0° C. for 30 minutes, then diluted with dichloromethane (170 ml). Acetic anhydride (48.3 ml, 510.98 mmol) in dichloromethane (100 ml) was added dropwise at 0° C. After addition, the reaction was warmed to room temperature and stirred at room temperature for 8 hours. Saturated sodium bicarbonate solution (50 ml) was added and extracted with EtOAc (2×200 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 (26.6 g, 35%). 1H NMR (400 MHz) δ 9.37 (s, 1H), 8.57 (d, J=2.8 Hz, 1H), 7.81 (m, 2H), 6.01 (s, 1H), 5.52 (s, 1H), 2.08 (s, 3H). MS: Calculated: 180. Found: [M+H]+ 181.

Workup

  1. additionAfter addition
  2. temperaturethe reaction was warmed to room temperature
  3. stirringstirred at room temperature for 8 hours
  4. extractionextracted with EtOAc (2×200 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-2cb0d9bce6b245fa8f66b962800bb6c7
Source dataset
uspto-grants-2013_07
Patent number
US08486966B2

Reaction notes

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