ChemicalBook CAS DataBase List 7-BROMO-2-CHLORO-QUINOLINE

7-BROMO-2-CHLORO-QUINOLINE synthesis

9synthesis methods

Product Name:7-BROMO-2-CHLORO-QUINOLINE
CAS Number:99455-15-9
Molecular formula:C9H5BrClN
Molecular Weight:242.5

99465-10-8 Synthesis

99465-10-8
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$22.00/100mg

99455-15-9
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$12.00/100mg

Yield: 78.8%

Reaction Conditions:

Stage #1:7-bromo-quinolin-2-ol with thionyl chloride in dichloromethane;N,N-dimethyl-formamide for 2 h;Heating / reflux;
Stage #2: in dichloromethane;water;N,N-dimethyl-formamide; pH=> 7

Steps:

6
Example 6 Preparation of Compound of Formula (VIII): 7-Bromo-2-chloroquinoline. An inerted reactor equipped with a mechanical stirrer, a reflux condenser, an addition funnel and caustic scrubber was charged with 7-bromo-2-hydroxyquinoline (1.22 Kg, 5.45 mole), dichloromethane (9.706 Kg), and dimethylformamide (0.276 Kg) followed by a slow addition of thionyl chloride (0.973 Kg, 8.17 mole, 1.5 equiv.). The reaction mixture was then gradually heated to reflux. The reflux was continued until solution is achieved (about 2 hours). The reaction mixture was then cooled to 20 to 25°C, and USP purified water (3.663 Kg) was added and stirred. Then to the reactor was gradually added with stirring a solution of potassium carbonate (0.828 Kg) in USP purified water (0.828 Kg). After 15 minutes, the stirring was stopped and the layers were allowed to separate. The pH of aqueous layer was confirmed greater than 7. The dichloromethane solution was separated and washed with USP purified water (3.663 Kg). USP purified water (7.326 Kg) was then added to the dichloromethane solution, and the dichloromethane was distilled off until the product precipitated out of the aqueous layer. The reactor was cooled to 20 to 25°C. The product was filtered and washed USP purified water (2 x 1.22 Kg). The product was dried in a vacuum oven at 40 to 5O⁰C to obtain 1.154 Kg of desired product. Yield: 78.8%. NMR: Compatible with product.

References:

SANOFI-AVENTIS U.S. LLC WO2009/2955, 2008, A1 Location in patent:Page/Page column 10