Phosphorus oxychloride → 3-Chloro-6-(4-fluorophenyl)-1,2,4-triazine

HRID 1257765Notes

Reaction equation

HRID 1257765 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[N:10][C:11](=O)[NH:12][N:13]=2)=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:17])=O>C(Cl)(Cl)Cl>[Cl:17][C:11]1[N:12]=[N:13][C:8]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)=[CH:9][N:10]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 125812846-(4-Fluorophenyl)-1,2,4-triazin-3(2H)-one

Product 1

HCID 213152193-Chloro-6-(4-fluorophenyl)-1,2,4-triazine

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

A mixture of 6-(4-fluorophenyl)-1,2,4-triazin-3(2H)-one (1.0 g, 5.23 mmol) and phosphoryl chloride (8.0 mL) in chloroform (5.0 mL) was heated under reflux conditions overnight. After cooling, the volatiles were removed under reduced pressure. The residue was dissolved in dichloromethane (60 mL) and was poured into ice with stirring. The mixture was neutralized with aqueous 2N potassium carbonate and filtered through a pad of Celite. The organic layer was separated and the aqueous layer was extracted with dichloromethane (3×20 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography to give the desired product. (600 mg, 54.6%) 1H-NMR (300 MHz, CDCl3): 8.88 (s, 1H), 8.06-8.12 (m, 2H), 7.06-7.14 (m, 2H). LCMS: (M+H)=210.1/212.1.

Workup

  1. temperaturewas heated under reflux conditions overnight
  2. temperatureAfter cooling
  3. customthe volatiles were removed under reduced pressure
  4. dissolutionThe residue was dissolved in dichloromethane (60 mL)
  5. additionwas poured into ice
  6. filtrationfiltered through a pad of Celite
  7. customThe organic layer was separated
  8. extractionthe aqueous layer was extracted with dichloromethane (3×20 mL)
  9. dry with materialThe combined organic extracts were dried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-41c44009e0234d038008db95a390e716
Source dataset
uspto-grants-2013_06
Patent number
US08461330B2

Reaction notes

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