Phosphorus oxychloride → HCID 86715649, compound

HRID 1507296Notes

Reaction equation

HRID 1507296 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH2:12][CH3:13])[C:6]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=1)=[C:5]2O.P(Cl)(Cl)([Cl:28])=O>C(#N)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH2:12][CH3:13])[C:6]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=1)=[C:5]2[Cl:28]

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178437400HCID 178437400, compound2×

Product 1

HCID 86715649HCID 86715649, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

A round-bottomed flask containing a mixture of 6-bromo-2-ethyl-3-(4-(trifluoromethyl)benzyl)quinolin-4-ol (4.00 g, 8.29 mmol, Intermediate 5: step b), phosphorous oxychloride (3.50 mL, 37.3 mmol) and acetonitrile (27 mL) was placed into a metal heating block at 90° C. After 65 minutes, the reaction mixture was cooled to room temperature. The acetonitrile and excess phosphorous oxychloride were removed by rotary evaporation. The residue was dissolved in dichloromethane (100 mL) and the solution was cooled in an ice-water bath. Ice (50 mL) was added. Concentrated aqueous ammonia solution was added dropwise until the pH=8-9 by litmus paper test. The biphasic mixture was separated and the aqueous layer was extracted with dichloromethane (50 mL). The combined organics were dried with sodium sulfate and the dried solution was filtered. Silica gel (8 g) was added to the filtrate and the solvents were removed by rotary evaporation to provide a free-flowing powder. The powder was loaded onto a silica gel column. Elution with hexanes initially, grading to 20% ethyl acetate-hexanes provided the title compound as an off-white solid.

Workup

  1. additionA round-bottomed flask containing
  2. temperaturethe reaction mixture was cooled to room temperature
  3. customThe acetonitrile and excess phosphorous oxychloride were removed by rotary evaporation
  4. dissolutionThe residue was dissolved in dichloromethane (100 mL)
  5. temperaturethe solution was cooled in an ice-water bath
  6. additionIce (50 mL) was added
  7. additionConcentrated aqueous ammonia solution was added dropwise until the pH=8-9 by litmus paper test
  8. customThe biphasic mixture was separated
  9. extractionthe aqueous layer was extracted with dichloromethane (50 mL)
  10. dry with materialThe combined organics were dried with sodium sulfate
  11. filtrationthe dried solution was filtered
  12. additionSilica gel (8 g) was added to the filtrate
  13. customthe solvents were removed by rotary evaporation
  14. customto provide a free-flowing powder
  15. washElution with hexanes initially

Sources & evidence

ORD record
ord-63cd54fc976e4886bba8939cdf2fc215
Source dataset
uspto-grants-2015_12
Patent number
US09221804B2

Reaction notes

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