Potassium Carbonate → 3-Chloro-4-(6-methoxyquinolin-2-yl)benzoic acid

Participants

Role	Name	HCID	Charge
Reactant	Potassium Carbonate	HCID 11430	—
Reactant	2-Chloro-6-methoxyquinoline	HCID 83647	—
Reactant	Simtuzumab	HCID 17750227	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Ethyl Acetate	HCID 8857	—
Solvent	Degme H2O	HCID 49835946	—
Product	3-Chloro-4-(6-methoxyquinolin-2-yl)benzoic acid	HCID 66980063	46%

Reaction Conditions

Temperature	110 °C

Reaction Steps

A mixture of 2-chloro-6-methoxyquinoline (Intermediate 1) (200 mg, 1.04 mmol), 4-carboxy-2-chlorophenylboronic acid (247 mg, 1.24 mmol) and K2CO3 (369 mg, 2.70 mmol) in DEGME/H2O (7.0 mL/2.0 mL) was degassed three times under N2 atmosphere. Then PdCl2(dppf) (75 mg, 0.104 mmol) was added and the mixture was heated to 110° C. for 3 hours under N2 atmosphere. The reaction mixture was diluted with EtOAc (100 mL) and filtered. The filtrate was washed with brine (20 mL), dried over Na2SO4, filtered and concentrated to give 3-chloro-4-(6-methoxyquinolin-2-yl)benzoic acid (150 mg, yield 46%) as a yellow solid, which was used for the next step without further purification.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09012646B2
Source dataset	uspto-grants-2015_04
ORD ID	ord-305c57c7bb87415f8f3ec0848b838a06
Source note	uspto-grants-2015_04