Acetic Anhydride → N-(1-(3,5-difluoropyridin-2-yl)vinyl)acetamide

HRID 75948Notes

Reaction equation

HRID 75948 reaction equation
[F:1][C:2]1[C:3](/[C:9](=[N:11]\O)/[CH3:10])=[N:4][CH:5]=[C:6]([F:8])[CH:7]=1.[C:13](OC(=O)C)(=[O:15])[CH3:14]>CN(C=O)C.CCOCC.[Fe].C[Si](Cl)(C)C>[F:1][C:2]1[C:3]([C:9]([NH:11][C:13](=[O:15])[CH3:14])=[CH2:10])=[N:4][CH:5]=[C:6]([F:8])[CH:7]=1

Participants

7

Reactant 2

HCID 7918Acetic AnhydrideHCID 136068547(NZ)-N-[1-(3,5-difluoro-2-pyridinyl)ethylidene]hydroxylamine

Product 1

HCID 66736036N-(1-(3,5-difluoropyridin-2-yl)vinyl)acetamideYield 19%

Reagents, catalysts & solvents 4

HCID 6397ChlorotrimethylsilaneCatalystHCID 23925IronCatalystHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of (Z)-1-(3,5-difluoropyridin-2-yl)ethanone oxime (Method 54, 12.5 g, 72.6 mmol), acetic anhydride (54.8 ml, 581 mmol), and iron powder (32.4 g, 581 mmol) in DMF (100 ml) was added TMSCl (0.01 ml, 0.073 mmol). The reaction mixture was stirred at room temperature for 18 hours, then diluted with ether (300 ml) and filtered through a short pad of celite. The filtrate was concentrated and the residue was partitioned between 200 ml of EtOAc and 50 ml of saturated sodium bicarbonate. The organic layer was separated and dried over sodium sulfate. After removal of solvent, the resulted residue was purified by column chromatography (hexane-EtOAc=2:1) to give the title compound as a white solid (2.70 g, 19%). 1H NMR (400 MHz) δ 9.55 (s, 1H), 8.51 (d, J=2.0 Hz, 1H), 7.97 (m, 1H), 5.87 (s, 1H), 5.14 (s, 1H), 1.99 (s, 3H). MS: Calcd.: 198. Found: [M+H]+ 199.

Workup

  1. filtrationfiltered through a short pad of celite
  2. concentrationThe filtrate was concentrated
  3. customthe residue was partitioned between 200 ml of EtOAc and 50 ml of saturated sodium bicarbonate
  4. customThe organic layer was separated
  5. dry with materialdried over sodium sulfate
  6. customAfter removal of solvent
  7. customthe resulted residue was purified by column chromatography (hexane-EtOAc=2:1)

Sources & evidence

ORD record
ord-bcfbda1a855a40d1b406f92139cc1a4e
Source dataset
uspto-grants-2014_09
Patent number
US08835465B2

Reaction notes

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