反应详情

温度

80 °C

To the paste-like solid obtained from Step 1 in a 4-neck round bottomed flask (500 mL) was added chlorobenzene (120 mL). Phosphoryl chloride (10.2 mL, 0.110 mol) was added dropwise to the thick mixture over 10 minutes. The temperature of the mixture went from 22° C. to 27° C. The slurry was heated at 80° C. for 1 hour. The mixture was cooled to 25° C., water (120 mL) was added to dissolve the solids, and the temperature rose to 28° C. The two phase mixture was brought to pH ˜12 with sodium hydroxide (50% in water, 42.8 g) using an ice-bath cooling to keep the temperature below 40° C. After cooling to 30° C., the mixture was transferred to a separatory funnel. The phases separated rapidly, and the bottom aqueous layer (containing some suspended solids) was removed from the dark organic phase. Attempted re-extraction of the aqueous phase with chlorobenzene (30 mL) resulted in an emulsion with solids present. The mixture was filtered through Celite®, the phases allowed to settle, and the organics added to the above organic phase to give a solution of the title compound as a dark amber liquid containing a small amount of fine solids (319 g, LC internal standard analysis indicated 4.3 wt % (75.4 mmol) 3-chloro-4,5-dihydro-1-(3-pyridinyl)-1H-pyrazole in the solution, for an in-pot yield of 75% starting from 3-hydrazinopyridine).

1. customwent from 22° C. to 27° C
2. temperatureThe mixture was cooled to 25° C.
3. dissolutionto dissolve the solids
4. customrose to 28° C
5. temperaturecooling
6. customthe temperature below 40° C
7. temperatureAfter cooling to 30° C.
8. customthe mixture was transferred to a separatory funnel
9. customThe phases separated rapidly
10. additionthe bottom aqueous layer (containing some suspended solids)
11. customwas removed from the dark organic phase
12. extractionAttempted re-extraction of the aqueous phase with chlorobenzene (30 mL)
13. customresulted in an emulsion with solids present
14. filtrationThe mixture was filtered through Celite®
15. additionthe organics added to the above organic phase