Reaction #84063

Reaction equation

2-chloro-6-methoxyquinoline

Intermediate 1

2-chloro-6-methoxyquinoline

4-carboxy-2-chlorophenylboronic acid

K2CO3

→

3-chloro-4-(6-methoxyquinolin-2-yl)benzoic acid

Yield 46.0%

Solvents

EtOAc

DEGME H2O

Conditions

Workup

1. 1
   Otherwas degassed three times under N2 atmosphere
2. 2
   Filtrationfiltered
3. 3
   WashThe filtrate was washed with brine (20 mL)
4. 4
   Dryingdried over Na2SO4
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated

Procedure

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.

Source