1,1'-Carbonyldiimidazole → 3-Fluoro-N-methoxy-N-methylpicolinamide

HRID 573348Notes

Reaction equation

HRID 573348 reaction equation
[F:1][C:2]1[C:3]([C:8]([OH:10])=O)=[N:4][CH:5]=[CH:6][CH:7]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.Cl.[CH3:24][NH:25][O:26][CH3:27].CCN(C(C)C)C(C)C>C1COCC1>[F:1][C:2]1[C:3]([C:8]([N:25]([O:26][CH3:27])[CH3:24])=[O:10])=[N:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 27627863-Fluoropyridine-2-carboxylic acid

Product 1

HCID 866889893-Fluoro-N-methoxy-N-methylpicolinamideYield 94.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 3-fluoropicolinic acid (17.7 g) in THF (300 mL) was added CDI (22.4 g) at room temperature, and the mixture was stirred at room temperature for 30 min and heated to 50° C. After stirring at 50° C. for 1 h, the mixture was cooled to room temperature. To the mixture were added N,O-dimethylhydroxylamine hydrochloride (18.4 g) and DIPEA (32.9 mL) at room temperature, and the mixture was stirred at room temperature for 12 h. The mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (AcOEt) to give the title compound (21.8 g).

Workup

  1. temperatureheated to 50° C
  2. stirringAfter stirring at 50° C. for 1 h
  3. temperaturethe mixture was cooled to room temperature
  4. stirringthe mixture was stirred at room temperature for 12 h
  5. concentrationThe mixture was concentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (AcOEt)

Sources & evidence

ORD record
ord-2b5f36724e144136bb7fb640ab418644
Source dataset
uspto-grants-2015_05
Patent number
US09029536B2

Reaction notes

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