1,2-Dichlorobenzene → 2-Bromo-5-(4-fluorophenyl)-4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)pyridine

HRID 234711

반응식

HRID 234711 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([C:19]3[CH:24]=[CH:23][C:22]([S:25]([CH3:28])(=[O:27])=[O:26])=[CH:21][CH:20]=3)=[CH:10][C:11](=O)[NH:12][C:13]=2[C:14]([F:17])([F:16])[F:15])=[CH:4][CH:3]=1.P(Br)(Br)(Br)(Br)[Br:30].[Br-].[K+].ClC1C=CC=CC=1Cl>C(Cl)Cl.O>[Br:30][C:11]1[CH:10]=[C:9]([C:19]2[CH:24]=[CH:23][C:22]([S:25]([CH3:28])(=[O:27])=[O:26])=[CH:21][CH:20]=2)[C:8]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)=[C:13]([C:14]([F:17])([F:16])[F:15])[N:12]=1

참가 물질

7

반응물 4

HCID 72391,2-DichlorobenzeneHCID 62678Phosphorus pentabromide2회HCID 253877Potassium BromideHCID 233552585-(4-Fluorophenyl)-4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)-2-oxo-pyridine

생성물 1

HCID 102770962-Bromo-5-(4-fluorophenyl)-4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)pyridine수율 37.2%

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매

실험 절차

A mixture of 0.35 g of 5-(4-fluorophenyl)-4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)-2-oxo-pyridine (step 5 of Example 1), 3 g of phosphorus pentabromide, 0.3 g of potassium bromide and 10 mL of 1,2-dichlorobenzene was held at reflux for 2 hours. The reaction mixture was cooled. An addition 3.7 g of phosphorus pentabromide was added to the reaction mixture and the reaction mixture was held at 90° C. for 8 hours, and at 180°-190° C. for 2 days. The reaction mixture was cooled and stirred with water and methylene chloride. The methylene chloride layer was dried over MgSO4 and filtered through silica gel. The methylene chloride filtrate was concentrated in vacuo and the residue was purified by HPLC (20% ethyl acetate/hexane then 50% ethyl acetate/hexane). The fraction eluted with 50% ethyl acetate/hexane yielded a solid. Recrystallization from methylene chloride/hexane yielded 150 mg of white solid: mp 187.5°-189° C.

후처리

  1. temperatureat reflux for 2 hours
  2. temperatureThe reaction mixture was cooled
  3. additionwas added to the reaction mixture
  4. waitat 180°-190° C. for 2 days
  5. temperatureThe reaction mixture was cooled
  6. dry with materialThe methylene chloride layer was dried over MgSO4
  7. filtrationfiltered through silica gel
  8. concentrationThe methylene chloride filtrate was concentrated in vacuo
  9. customthe residue was purified by HPLC (20% ethyl acetate/hexane
  10. washThe fraction eluted with 50% ethyl acetate/hexane
  11. customyielded a solid
  12. customRecrystallization from methylene chloride/hexane

출처 및 근거

ORD 기록
ord-9f4fb3f797e6435ba01617398cd780ee
출처 데이터셋
uspto-grants-1997_01
특허 번호
US05596008

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