Phosphorus oxychloride → 2-Chloro-4-(4-trifluoromethylphenyl)pyridine

HRID 730313Notes

Reaction equation

HRID 730313 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][N+:12]([O-])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.P(Cl)(Cl)([Cl:20])=O>>[Cl:20][C:13]1[CH:14]=[C:9]([C:6]2[CH:7]=[CH:8][C:3]([C:2]([F:17])([F:16])[F:1])=[CH:4][CH:5]=2)[CH:10]=[CH:11][N:12]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 573508294-(4-(Trifluoromethyl)phenyl)pyridine 1-oxide

Product 1

HCID 288758632-Chloro-4-(4-trifluoromethylphenyl)pyridine

Procedure

To 4-(4-trifluoromethyl-phenyl)-pyridine 1-oxide (2.4 g, 10 mmol) was added phosphorous oxychloride (12 mL) at room temperature. The reaction mixture was heated at reflux for 5 h. POCl3 was removed under reduced pressure, and the residue was partitioned between EtOAc and aqueous ammonium hydroxide. The aqueous layer was extracted with EtOAc and the combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The crude material was purified by chromatography on a Biotage 40 M column (8:1 hexanes:EtOAc) to give the title compound as a white solid. MS (ESI, pos. ion) m/z: 258.5 (M+1).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 5 h
  3. customPOCl3 was removed under reduced pressure
  4. customthe residue was partitioned between EtOAc and aqueous ammonium hydroxide
  5. extractionThe aqueous layer was extracted with EtOAc
  6. dry with materialthe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude material was purified by chromatography on a Biotage 40 M column (8:1 hexanes:EtOAc)

Sources & evidence

ORD record
ord-b9880877cfc945ae9dd7d354a2c150a8
Source dataset
uspto-grants-2009_09
Patent number
US07582657B2

Reaction notes

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