反应详情

温度

55 °C

A 2 L 3-neck flask was charged with 3-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-4-hydroxy-phenyl]-propionic acid tert-butyl ester (67.9 g, 0.178 mol), toluene-4-sulfonic acid 2-(5-methyl-2-phenyl-oxazol-4-yl)-ethyl ester (76.6 g, 0.214 mol) and DMF (680 mL). Cesium carbonate (75.4 g, 0.231 mol) was added, and the reaction mixture was heated at 55° C. for 18 h. After cooling, ethyl acetate (890 mL) and DI water (1200 mL) were added, the mixture was agitated, and the layers were separated. The aqueous layer was back-extracted with ethyl acetate (740 mL). The organic layers were combined and washed with 1N NaOH (375 mL) then saturated NaCl solution (2×375 mL). The organic solution was dried (Na2SO4), filtered, and concentrated to an oil (107 g). The crude oil was dissolved in toluene (50 mL), and heptane was added (˜100 mL) until cloudiness remained even with agitation. The mixture was warmed to 50° C. on a rotary evaporator to yield a solution. Seed crystals were added, and rotation was continued at ambient temperature overnight. The product slurry was placed in the freezer overnight and filtered. The title compound was dried in a vacuum oven at 35° C. (71.4 g, 70.8%).

1. temperatureAfter cooling
2. customthe layers were separated
3. extractionThe aqueous layer was back-extracted with ethyl acetate (740 mL)
4. washwashed with 1N NaOH (375 mL)
5. dry with materialThe organic solution was dried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated to an oil (107 g)
8. dissolutionThe crude oil was dissolved in toluene (50 mL)
9. additionheptane was added (˜100 mL) until cloudiness
10. temperatureThe mixture was warmed to 50° C. on a rotary evaporator
11. customto yield a solution
12. additionSeed crystals were added
13. customwas placed in the freezer overnight
14. filtrationfiltered
15. dry with materialThe title compound was dried in a vacuum oven at 35° C. (71.4 g, 70.8%)