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

HRID 383565노트

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HRID 383565 반응식
Cl.[F:2][C:3]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:4]=1[NH:10][NH2:11].CCN(CC)CC.C(N(CC(O)=O)CC(O)=O)CN(CC([O-])=O)CC([O-])=O.O.O.[Na+].[Na+].Cl[C:44](=[CH2:47])[C:45]#[N:46].S(=O)(=O)(O)O>CO>[F:2][C:3]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:4]=1[N:10]1[C:45]([NH2:46])=[CH:44][CH:47]=[N:11]1

참가 물질

7

반응물 5

HCID 1118Sulfuric AcidHCID 8471TriethylamineHCID 701982-ChloroacrylonitrileHCID 27333012,4-Difluorophenylhydrazine hydrochlorideHCID 44120005Edta disodium

생성물 1

HCID 433167681-(2,4-Difluorophenyl)-1H-pyrazol-5-amine

시약·촉매·용매 1

HCID 887Methanol용매

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온도
70 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-827d822dab2c4eb19f00a53b1c9daf2f
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08367671B2

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