反应详情

A 30-gallon, glass-lined reactor was charged with 3-(4-fluoro-phenoxy)-iodobenzene (10.0 kg), copper(I) iodide (60.6 g), triphenyl-phosphine (95.0 g), bis(acetonitrile)palladium(II) chloride, and methyl t-butyl ether (27 kg). The mixture was cooled to 0°-10° C. and 55% aqueous 3-butyn-2-ol (4.20 kg) was added. Diisopropylamine (3.8 kg) was added to initiate the reaction and N2 was bubbled up from the bottom valve for a few minutes to agitate the reaction mixture. The reaction mixture was agitated at 15°-25° C. for 1.5 hours and then quenched by addition of 28% aqueous ammonia (12 kg) and brine (30 kg). The layers were separated and the organic phase was washed sequentially with brine (35 kg), 10% aqueous HCl (18 kg), 10% aqueous NaHCO3 (18 kg), and brine (35 kg). The organic phase was then stirred for 45 minutes with anhydrous MgSO4 (1.5 kg), PWA carbon (1.0 kg), and Ultra Norit C (1.0 kg) and filtered to give a solution of 4-[3-(4-fluorophenoxy)phenyl]-3-butyn-2-ol in methyl t-butyl ether which was used in the next step.

1. temperatureThe mixture was cooled to 0°-10° C.
2. customwas bubbled up from the bottom valve for a few minutes
3. stirringThe reaction mixture was agitated at 15°-25° C. for 1.5 hours
4. customquenched by addition of 28% aqueous ammonia (12 kg) and brine (30 kg)
5. customThe layers were separated
6. washthe organic phase was washed sequentially with brine (35 kg), 10% aqueous HCl (18 kg), 10% aqueous NaHCO3 (18 kg), and brine (35 kg)
7. stirringThe organic phase was then stirred for 45 minutes with anhydrous MgSO4 (1.5 kg), PWA carbon (1.0 kg), and Ultra Norit C (1.0 kg)
8. filtrationfiltered