Sulfuric Acid → 1-(2,4-Difluorophenyl)-1H-pyrazol-5-amine

温度

70 °C

A 250 mL RBF containing a solution of 1-(2,4-difluorophenyl)hydrazine hydrochloride (10.33 g, 57 mmol), Et3N (8.0 mL, 57 mmol), EDTA disodium salt dihydrate (50 mg, 0.13 mmol) in 100 mL of MeOH was fitted with a reflux condenser, and heated to 70° C. To the refluxing solution was added 2-chloroacrylonitrile (5.0 mL, 57 mmol) slowly. The solution was heated at reflux for an additional 7.5 h. It was cooled to RT then concentrate sulfuric acid (5.2 mL, 97 mmol) was added slowly and the reaction mixture again heated to reflux for 18 h. The reaction mixture was cooled to 0° C. and treated with Na2CO3 monohydrate (21.00 g) and stirred at RT for 8 h. The reaction mixture was concentrated on the rotovap to remove the MeOH. The resulting rust colored solid was then treated with 100 mL of water and extracted with EtOAc (2×100 mL). The combined EtOAc layers were washed with brine, dried and concentrated. Purification of the crude material on an ISCO 120 g column (20-80% EtOAc in hexanes) afforded 1-(2,4-difluorophenyl)-1H-pyrazol-5-amine as an orange-brown viscous oil. MS (ES+): 196.1 (M+H)+. A further general description of this procedure can be found in U.S. Pat. No. 4,803,215.

1. customwas fitted with a reflux condenser
2. temperatureThe solution was heated
3. temperatureat reflux for an additional 7.5 h
4. temperatureIt was cooled to RT
5. temperaturethe reaction mixture again heated
6. temperatureto reflux for 18 h
7. temperatureThe reaction mixture was cooled to 0° C.
8. concentrationThe reaction mixture was concentrated on the rotovap
9. customto remove the MeOH
10. additionThe resulting rust colored solid was then treated with 100 mL of water
11. extractionextracted with EtOAc (2×100 mL)
12. washThe combined EtOAc layers were washed with brine
13. customdried
14. concentrationconcentrated
15. customPurification of the crude material on an ISCO 120 g column (20-80% EtOAc in hexanes)

ORDレコード

ord-827d822dab2c4eb19f00a53b1c9daf2f

出典データセット

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08367671B2