Ethyl Acetate → 2,5-Difluoro-N-methoxy-N-methylnicotinamide

HRID 715916Notes

Reaction equation

HRID 715916 reaction equation
[F:1][C:2]1[C:7]([C:8](O)=[O:9])=[CH:6][C:5]([F:11])=[CH:4][N:3]=1.Cl.C(N=C=NCCCN(C)C)C.Cl.[CH3:25][NH:26][O:27][CH3:28].C(OCC)(=O)C>CN(C)C=O.C(N(C(C)C)CC)(C)C.ON1C2C=CC=CC=2N=N1.O>[F:1][C:2]1[C:7]([C:8]([N:26]([O:27][CH3:28])[CH3:25])=[O:9])=[CH:6][C:5]([F:11])=[CH:4][N:3]=1

Participants

9

Reactant 4

HCID 8857Ethyl AcetateHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 118159992,5-difluoropyridine-3-carboxylic Acid

Product 1

HCID 916189642,5-Difluoro-N-methoxy-N-methylnicotinamideYield 63.5%

Reagents, catalysts & solvents 4

HCID 757711-HydroxybenzotriazoleCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 81531DiisopropylethylamineSolvent

Procedure

To a solution of 2,5-difluoropyridine-3-carboxylic acid (3.00 g), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (4.34 g), 1-hydroxybenzotriazole (127 mg), and N,O-dimethylhydroxylamine hydrochloride (1.93 g) in N,N-dimethylformamide (30 ml), diisopropylethylamine (7.42 ml) was added, and the mixture was stirred overnight at room temperature. Ethyl acetate and water were added to the reaction solution to separate the aqueous and organic layers. The aqueous layer was subjected to extraction with ethyl acetate. The organic layers were combined, washed with saturated saline, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain the title compound (2.42 g).

Workup

  1. customto separate the aqueous and organic layers
  2. extractionThe aqueous layer was subjected to extraction with ethyl acetate
  3. washwashed with saturated saline
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-264b2750b84c4af2b44b8bbf3e1a064d
Source dataset
uspto-grants-2015_11
Patent number
US09187489B2

Reaction notes

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