4-Methylmorpholine → 2-Chloro-N-methoxy-N-methylisonicotinamide

Participants

Role	Name	HCID	Charge
Reactant	4-Methylmorpholine	HCID 7972	—
Reactant	Methanamine, N-methoxy-, hydrochloride (1:1)	HCID 81138	—
Reactant	2-Chloroisonicotinic acid	HCID 236985	—
Reactant	1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride	HCID 2723939	—
Catalyst	4-(Dimethylamino)pyridine	HCID 14284	—
Solvent	Water	HCID 962	—
Solvent	Dichloromethane	HCID 6344	—
Product	2-Chloro-N-methoxy-N-methylisonicotinamide	HCID 18506894	97.7%

Reaction Conditions

Temperature	0 °C

Reaction Steps

To a suspension of 2-chloroisonicotinic acid (20 g, 0.127 mol), N,O-dimethyl-hydroxylamine HCl (19.8 g, 0.203 mol), 4-methylmorpholine (20.5 g, 0.203 mol) and DMAP (1.55 g, 0.013 mol) in dichloromethane (300 ml) at 0° C. was added EDCI HCl (29.2 g, 0.152 mol). The mixture was stirred at 0° C. for 10 min and at room temperature for 17 h. The mixture was poured into water/1M aqueous HCl and extracted with dichloromethane. The combined organic phases were washed with water, saturated aqueous NaHCO3 solution and brine. The organic layer was dried over MgSO4, filtered and concentrated to give the title compound (24.9 g) as a white solid. MS(m/e)=201.2 [M+H+].

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08138189B2
Source dataset	uspto-grants-2012_03
ORD ID	ord-3512f20f28114edd83377bf829793810
Source note	uspto-grants-2012_03