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

HRID 234711

Reaction equation

HRID 234711 reaction equation
[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

Participants

7

Reactant 4

HCID 72391,2-DichlorobenzeneHCID 62678Phosphorus pentabromide2×HCID 253877Potassium BromideHCID 233552585-(4-Fluorophenyl)-4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)-2-oxo-pyridine

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-9f4fb3f797e6435ba01617398cd780ee
Source dataset
uspto-grants-1997_01
Patent number
US05596008

Linked notes

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