1,1'-Carbonyldiimidazole → 3,5-difluoro-N-methoxy-N-methylpicolinamide

HRID 573339Notes

Reaction equation

HRID 573339 reaction equation
[F:1][C:2]1[C:3]([C:9]([OH:11])=O)=[N:4][CH:5]=[C:6]([F:8])[CH:7]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.Cl.[CH3:25][NH:26][O:27][CH3:28].CCN(C(C)C)C(C)C>C1COCC1>[F:1][C:2]1[C:3]([C:9]([N:26]([O:27][CH3:28])[CH3:25])=[O:11])=[N:4][CH:5]=[C:6]([F:8])[CH:7]=1

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 27832623,5-Difluoropyridine-2-carboxylic acid

Product 1

HCID 866889883,5-difluoro-N-methoxy-N-methylpicolinamideYield 56.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a suspension of 3,5-difluoropicolinic acid (3.5 g) in THF (70 ml) was added CDI (3.92 g) at room temperature. The mixture was stirred at room temperature for 30 min and at 50° C. for 1 h. After cooling to room temperature, N,O-dimethylhydroxylamine hydrochloride (3.22 g) and DIPEA (5.76 mL) were added. The mixture was stirred at room temperature for 12 h, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/AcOEt) to give the title compound (2.5 g).

Workup

  1. temperatureAfter cooling to room temperature
  2. stirringThe mixture was stirred at room temperature for 12 h
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (hexane/AcOEt)

Sources & evidence

ORD record
ord-6ff13c8000194879a37f3a0e314f8e53
Source dataset
uspto-grants-2015_05
Patent number
US09029536B2

Reaction notes

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