反应详情

温度

20.5 °C

A 5 L 3 neck, round bottom flask was inerted and charged with CDI (153 g, 0.94 mol, 1.2 equiv), 4-(Octyloxy)-3-(trifluoromethyl)benzoic acid (D5A) (250 g based on theoretical output of previous step, 0.78 mol), THF (2.5 L) and stirred at 18 to 23° C. for 1 hour. A separate 12 L round bottom flask was inerted and charged with hydrazine monohydrate (235 g, 4.71 mol, 6 equiv) and THF (1.2 L). The contents of the first flask was charged to the second flask over 1 hour. During the addition, the temperature was maintained at T<25° C. Once the addition was complete, the mixture was stirred for 2 hours at 18 to 23° C., at which point TLC indicated the reaction was complete. The mixture was concentrated under vacuum at 35 to 40° C. until approximately 10 to 15% of the original volume was attained. Water (2 L) and brine (2 L) were charged to the mixture which was then extracted with dichloromethane (2×2.5 L). There was a small emulsion during each extraction. The organic phases were combined, washed with brine (500 mL), dried with magnesium sulfate, filtered over Celite, and concentrated to afford the title product (247 g, 94% yield, 96% AUC by HPLC) as a yellow solid.

1. customA separate 12 L round bottom flask was inerted
2. additionThe contents of the first flask was charged to the second flask over 1 hour
3. additionDuring the addition
4. temperaturethe temperature was maintained at T<25° C
5. additionOnce the addition
6. stirringthe mixture was stirred for 2 hours at 18 to 23° C., at which point TLC
7. concentrationThe mixture was concentrated under vacuum at 35 to 40° C. until approximately 10 to 15% of the original volume
8. additionWater (2 L) and brine (2 L) were charged to the mixture which
9. extractionwas then extracted with dichloromethane (2×2.5 L)
10. extractionduring each extraction
11. washwashed with brine (500 mL)
12. dry with materialdried with magnesium sulfate
13. filtrationfiltered over Celite
14. concentrationconcentrated