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ChemicalBook CAS DataBase List 8-bromo-5-fluoroquinoline
917251-99-1

8-bromo-5-fluoroquinoline synthesis

3synthesis methods
-

Yield: 89.8%

Reaction Conditions:

Stage #1:2-bromo-5-fluoroaniline;glycerol with sulfuric acid;sodium 3-nitrobenzenesulfonate in water at 60 - 130; for 3 h;
Stage #2: with sodium hydroxide in tert-butyl methyl ether;waterProduct distribution / selectivity;

Steps:

DD
1-(5-fluoroquinolin-8-yl)piperidin-4-one (Example P, Step 3) is also prepared as shown in the reaction scheme above. To a 500 ml flask equipped with a stirrer, a thermocouple, a condenser and nitrogen inlet were charged 50 g 2-bromo-5-fluoroaniline and 60 g glycerol. The mixture was heated to 60° C. and 55 g nitrobenzene sulfonic acid was charged in portion. The mixture was then heated to 100-110° C., started charge 200 ml 70% sulfuric acid. After sulfuric acid addition, the mixture was heat to 130° C. and stirred for 3 hours before cooled to room temperature. Water (300 g) was added and a grayish by product was filtered off. The filtrate was slowly added into a 2-L reactor containing a mix of 420 g 50% NaOH, 420 g of water, 352 g methyl tert-butyl ether. After filtering off small amount solid, the aqueous layer was split off and the organic layer was washed with 10% NaOH (2×100 ml), 20% NaCl (2×200 ml), the solvent was removed, weight 56 g, 89.8%.

References:

Wyeth US2007/27160, 2007, A1 Location in patent:Page/Page column 66

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