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

Participants

Role	Name	HCID	Charge
Reactant	1,1'-Carbonyldiimidazole	HCID 68263	—
Reactant	Methanamine, N-methoxy-, hydrochloride (1:1)	HCID 81138	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	3,5-Difluoropyridine-2-carboxylic acid	HCID 2783262	—
Solvent	Tetrahydrofuran	HCID 8028	—
Product	3,5-difluoro-N-methoxy-N-methylpicolinamide	HCID 86688988	56.2%

Reaction Conditions

Temperature	50 °C

Reaction Steps

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).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09029536B2
Source dataset	uspto-grants-2015_05
ORD ID	ord-6ff13c8000194879a37f3a0e314f8e53
Source note	uspto-grants-2015_05