反应详情

温度

74.5 °C

A 22-L straight wall reactor equipped with a mechanical stirrer was charged with tap water (3403 g). Dipotassium phosphate (K2HPO4; 2596 g, 14.9 mol) was then added, and the mixture was stirred until all solids dissolved while being purged with a nitrogen stream. After all the solids had dissolved, acetonitrile (8173 g) was loaded into the reactor. To a separate 30-L straight-wall jacketed reactor equipped with a bottom drain and a mechanical overhead stirrer was loaded 2-(4-chloro-2-fluoro-3-methoxyphenyl)-1,3,2-dioxaborinane (1724 g, 7.01 mol) and benzyl 4,5,6-trichloropicolinate (1630 g, 4.97 mol). The reactor was evacuated and filled with nitrogen (3×). The acetonitrile/H2O mixture containing K2HPO4 was then transferred into the 30-L reactor, and the lines were rinsed with acetonitrile (1434 g). The slurry was sparged with nitrogen for 30 min, and then triphenylphosphine (114.8 g, 0.44 mol) was added. The slurry was then sparged with nitrogen for 15 min followed by addition of bis(benzonitrile)palladium(II) chloride (83.8 g, 0.22 mol). The bright yellow slurry was sparged with nitrogen for 15 min, and then the mixture was heated to 74-75° C. After stirring at 74° C. for 3.3 h the reaction was deemed complete by HPLC analysis. At this stage the reactor cool-down temperature was set to 5° C. and immediately, cold water (4448 g, approximately 3° C.) was added to the reactor. The resulting precipitate was filtered to give a cream-white colored cake. The filter cake was washed with cold acetonitrile/H2O (3345 g, 1.4:1, 8-10° C.) to afford an off-white wet cake. The cake was dried under a stream of nitrogen to a constant weight of 2044 g. HPLC analysis using an internal standard (tetraphenylethylene) showed the product was 90.0% pure and contained 1840 g (84.0%) of the product.

1. customA 22-L straight wall reactor equipped with a mechanical stirrer
2. dissolutiondissolved
3. customwhile being purged with a nitrogen stream
4. dissolutionAfter all the solids had dissolved
5. customTo a separate 30-L straight-wall jacketed reactor equipped with a bottom drain and a mechanical overhead stirrer
6. customThe reactor was evacuated
7. additionfilled with nitrogen (3×)
8. additionThe acetonitrile/H2O mixture containing K2HPO4
9. washthe lines were rinsed with acetonitrile (1434 g)
10. customThe slurry was sparged with nitrogen for 30 min
11. customThe slurry was then sparged with nitrogen for 15 min
12. customThe bright yellow slurry was sparged with nitrogen for 15 min
13. stirringAfter stirring at 74° C. for 3.3 h the reaction
14. temperatureAt this stage the reactor cool-down temperature
15. customwas set to 5° C.
16. additionimmediately, cold water (4448 g, approximately 3° C.) was added to the reactor
17. filtrationThe resulting precipitate was filtered
18. customto give a cream-white colored cake
19. washThe filter cake was washed with cold acetonitrile/H2O (3345 g, 1.4:1, 8-10° C.)
20. customto afford an off-white wet cake
21. customThe cake was dried under a stream of nitrogen to a constant weight of 2044 g