Phosphorus oxychloride → HCID 83410607, compound

HRID 921631Notes

Reaction equation

HRID 921631 reaction equation
P(Cl)(Cl)(Cl)=O.[Br:6][C:7]1[CH:8]=[C:9]([CH:13]=[C:14]([Br:17])[C:15]=1[F:16])[C:10]([NH2:12])=O>C(#N)C>[Br:6][C:7]1[CH:8]=[C:9]([CH:13]=[C:14]([Br:17])[C:15]=1[F:16])[C:10]#[N:12]

Participants

4

Reactant 2

HCID 24813Phosphorus oxychloride2×HCID 86708486HCID 86708486, compound

Product 1

HCID 83410607HCID 83410607, compoundYield 118.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

(I14B): Phosphoryl trichloride (8.0 ml, 86 mmol) was added to a suspension of 3,5-dibromo-4-fluorobenzamide (11.27 g, crude, ˜22.7 mmol) in acetonitrile (400 ml) at room temperature. The reaction mixture was heated to reflux for 30 minutes. Additional phosphoryl trichloride (8.0 ml, 86 mmol) was added and the mixture heated to reflux for an additional hour, then stirred at room temperature overnight, A precipitate had formed and was removed by filtration. (The product is well soluble in acetonitrile) The reaction mixture was evaporated to dryness, and then partitioned between EtOAc and aq. NaHCO3 solution. The organic layer was washed one more time with aq. NaHCO3 solution, once with brine, then dried over MgSO4, filtered and evaporated to dryness. Purification by column chromatography on silica (gradient 100% hexanes to 25% DCM in hexanes). 3,5-dibromo-4-fluorobenzonitrile (7.5 g) was obtained. The material is (by 1H NMR and 19F NMR) a 76:17:7 mixture of 3,5-dibromo-4-fluorobenzonitrile (desired product), 2,3,5-tribromo-4-fluorobenzonitrile (over-bromination) and 2,5-dibromo-4-fluorobenzonitrile (wrong regio-isomer). The material was used without further purification in the next reaction.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 30 minutes
  3. temperaturethe mixture heated
  4. temperatureto reflux for an additional hour
  5. customA precipitate had formed
  6. customwas removed by filtration
  7. customwas evaporated to dryness
  8. custompartitioned between EtOAc and aq. NaHCO3 solution
  9. washThe organic layer was washed one more time with aq. NaHCO3 solution
  10. dry with materialonce with brine, then dried over MgSO4
  11. filtrationfiltered
  12. customevaporated to dryness
  13. customPurification by column chromatography on silica (gradient 100% hexanes to 25% DCM in hexanes)

Sources & evidence

ORD record
ord-627f3ed158d34c01801c1ef1d4a05e83
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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