Phosphorus oxychloride → HCID 86715646, compound

HRID 926488Notes

Reaction equation

HRID 926488 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH3:12])[C:6]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=1)=[C:5]2O.P(Cl)(Cl)([Cl:27])=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]([CH3:12])[C:6]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=1)=[C:5]2[Cl:27]

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178432087HCID 178432087, compound2×

Product 1

HCID 86715646HCID 86715646, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

A round-bottomed flask containing a mixture of 6-bromo-2-methyl-3-(4-(trifluoromethyl)benzyl)quinolin-4-ol (5.00 g, 12.6 mmol, Intermediate 26: step b), phosphorous oxychloride (5.90 mL, 63.1 mmol) and acetonitrile (42 mL) was warmed to 90° C. After 3 hours, the reaction mixture was cooled to room temperature. The acetonitrile and excess phosphorous oxychloride was removed by rotary evaporation. The residue was dissolved in dichloromethane (100 mL) and the solution was cooled in an ice-water bath. Ice (100 mL) was added. Concentrated aqueous ammonia solution was added dropwise until the pH=˜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 magnesium sulfate and the dried solution was filtered. Celite® (5 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 was 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 (100 mL) was added
  7. additionConcentrated aqueous ammonia solution was added dropwise until the pH=˜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 magnesium sulfate
  11. filtrationthe dried solution was filtered
  12. additionCelite® (5 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-470122d34cfe4aad9342ba756b31f9c6
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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