Methanol → Methyl 2-chloro-4-methylpyridine-3-carboxylate

https://huagongshe.com/reaction/1959594

Participants

Role	Name	HCID	Charge
Reactant	Methanol	HCID 887	—
Reactant	Methyl 4-bromo-2-chloronicotinate	HCID 44190945	—
Reactant	HCID 178477796	HCID 178477796	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	1,4-Dioxane	HCID 31275	—
Product	Methyl 2-chloro-4-methylpyridine-3-carboxylate	HCID 17862852	—

Reaction Conditions

Temperature	70 °C

Reaction Steps

ZnMe2 (2.0 M in toluene, 15.5 mL, 25 mmol) was added to a stirred mixture of 4-bromo-2-chloro-nicotinic acid methyl ester (9.6 g, 38 mmol) and Pd(dppf)Cl2 (0.50 g, 0.61 mmol) in anhydrous dioxane (180 mL). After stirring for 8 h at 70° C., the reaction mixture was cooled to room temperature, MeOH (15 mL) was added and the solvent was removed in vacuo. The residue was partitioned between EA (300 mL) and water (50 mL). Concentrated aqueous HCl was then added until the emulsion became homogeneous. The organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (elution with hexane/EA 2:1) to give the title compound. MS (m/z): 186.0 [M+H+].

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08410134B2
Source dataset	uspto-grants-2013_04
ORD ID	ord-9236a5a400ce455e88f05601d277935f
Source note	uspto-grants-2013_04