反应详情

温度

-70 °C

15 ml (24.00 mmol) of 1.6 molar n-butyllithium solution in hexane are added dropwise to a solution, cooled to -70° C., of 7.61 g (20.00 mmol) of 5-bromo-3-fluoro-2-(4-octyloxyphenyl)pyridine in 400 ml of tetrahydrofuran, and the mixture is stirred at -70° C. for 15 minutes. 7.5 g (40.00 mmol) of triisopropyl borate are subsequently added dropwise, the mixture is stirred at -70° C. for 1.5 hours and warmed to room temperature, 500 ml of ammonium chloride solution and 500 ml of ether are added, and the organic phase is separated off and washed twice with aqueous sodium chloride solution, dried over sodium sulfate and evaporated. The resultant 3-fluoro-2-(4-octyloxyphenyl)pyridine-5-boronic acid is refluxed for 2 hours in 100 ml of tetrahydrofuran with 30 ml of 17.5% strength by weight aqueous hydrogen peroxide solution and subsequently cooled to 0° C., and 200 ml of aqueous sodium sulfite solution are added dropwise. The organic phase is separated off, washed twice with aqueous sodium chloride solution, dried over sodium sulfate and evaporated to dryness. Recrystallization from 1,2-dichloroethane gives 5.08 g of 3-fluoro-5-hydroxy-2-(4-octyloxyphenyl)pyridine. ##STR17##

1. stirringthe mixture is stirred at -70° C. for 1.5 hours
2. temperaturewarmed to room temperature
3. customthe organic phase is separated off
4. washwashed twice with aqueous sodium chloride solution
5. dry with materialdried over sodium sulfate
6. customevaporated
7. temperatureThe resultant 3-fluoro-2-(4-octyloxyphenyl)pyridine-5-boronic acid is refluxed for 2 hours in 100 ml of tetrahydrofuran with 30 ml of 17.5% strength by weight aqueous hydrogen peroxide solution
8. temperaturesubsequently cooled to 0° C.
9. addition200 ml of aqueous sodium sulfite solution are added dropwise
10. customThe organic phase is separated off
11. washwashed twice with aqueous sodium chloride solution
12. dry with materialdried over sodium sulfate
13. customevaporated to dryness
14. customRecrystallization from 1,2-dichloroethane