反应详情

温度

105 °C

Ethyl 2-(2,3-difluoro-5-iodobenzoyl)-3-(2-formyl-2-methylhydrazino)prop-2-enoate (Preparation 30, 1.02 g) in 8 mL of water is treated with KOH pellets (0.410 g) and the reaction mixture is heated in an oil bath, under a nitrogen atmosphere, at 105° C. for 1.75 h while volatiles were condensed into a Dean-Stark trap. At this time, the Dean-Stark trap was removed, 1 mL of an aqueous solution of KOH (0.956 g) is added to the mixture, and heating is continued at 105° C. for 4 days. The mixture is cooled to room temperature, treated with formic acid (1.68 g), and is warmed to 45-50° C. A 37% aqueous formaldehyde (0.396 g) is added and the mixture is heated at 70° C. for 30 minutes. The resulting slurry is cooled in an ice bath at 0-5° C., reacted with 29% aqueous ammonium hydroxide (1.46 mL), and allowed to warm to room temperature where it is stirred for 35-40 minutes. Charcoal (44 mg) is added to the mixture which is stirred for 30 minutes and filtered through a pad of solka-floc rinsing with water. The filtrate is diluted with saturated brine and a mixture of chloroform/methanol (95/5) and filtered through a pad of solka-floc. The organic layer is separated, dried with anhydrous sodium sulfate, and concentrated at reduced pressure to obtain 252 mg (28%) of the title compound. Physical characteristics: MS (ESI+) m/z 373 (M+H)+.

1. customcondensed into a Dean-Stark trap
2. customAt this time, the Dean-Stark trap was removed
3. addition1 mL of an aqueous solution of KOH (0.956 g) is added to the mixture
4. temperatureheating
5. temperatureThe mixture is cooled to room temperature
6. additiontreated with formic acid (1.68 g)
7. temperatureis warmed to 45-50° C
8. additionA 37% aqueous formaldehyde (0.396 g) is added
9. temperaturethe mixture is heated at 70° C. for 30 minutes
10. temperatureThe resulting slurry is cooled in an ice bath at 0-5° C.
11. customreacted with 29% aqueous ammonium hydroxide (1.46 mL)
12. temperatureto warm to room temperature where it
13. stirringis stirred for 30 minutes
14. filtrationfiltered through a pad of solka-floc rinsing with water
15. additionThe filtrate is diluted with saturated brine
16. additiona mixture of chloroform/methanol (95/5)
17. filtrationfiltered through a pad of solka-floc
18. customThe organic layer is separated
19. dry with materialdried with anhydrous sodium sulfate
20. concentrationconcentrated at reduced pressure