Hydrochloric Acid → 4-(5-chloro-4-hydroxy-2-oxopyridin-1(2H)-yl)-2-fluorobenzonitrile

Participants

Role	Name	HCID	Charge
Reactant	Hydrochloric Acid	HCID 313	—
Reactant	Potassium Carbonate	HCID 11430	—
Reactant	2-Fluoro-4-iodobenzonitrile	HCID 2774518	—
Reactant	4,7-Dimethoxy-1,10-phenanthroline	HCID 10462298	—
Reactant	Gimeracil	HCID 54679224	—
Catalyst	Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)	HCID 24350	—
Solvent	Dimethyl Sulfoxide	HCID 679	—
Solvent	Water	HCID 962	—
Product	4-(5-chloro-4-hydroxy-2-oxopyridin-1(2H)-yl)-2-fluorobenzonitrile	HCID 67366532	74.7%

Reaction Conditions

Temperature	140 °C

Reaction Steps

A mixture of 2-fluoro-4-iodobenzonitrile (4000 mg, 16.19 mmol), 5-chloro-4-hydroxypyridin-2(1H)-one (2357 mg, 16.19 mmol), 4,7-dimethoxy-1,10-phenanthroline (778 mg, 3.24 mmol), copper(I) iodide (617 mg, 3.24 mmol) and potassium carbonate (4476 mg, 32.4 mmol) in DMSO (40 mL) was stirred at 140° C. under N2 for 3 h. After cooled to rt, the reaction mixture was diluted with H2O (50 mL) and added 1N HCl to adjust the pH to ˜2 (pH paper). The resulting mixture was extracted with EtOAc (400 mL, 2×). The combined extracts were dried (Na2SO4) and evaporated under reduced pressure to give black oil. The residue was purified by flash chromatography (SiO2, 0 to 7% MeOH/CH2Cl2) to give brown oil (3.2 g, 43.3%). MS (ESI) 265 (M+H).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08003796B2
Source dataset	uspto-grants-2011_08
ORD ID	ord-37030446caff4d4591107d96944c506f
Source note	uspto-grants-2011_08