Ammonium Chloride → HCID 136167025, compound

HRID 1617586Notes

Reaction equation

HRID 1617586 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[C:25]([F:28])([F:27])[F:26])[CH2:9][C:10]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([CH3:18])[CH:13]=2)=O)=[CH:4][CH:3]=1.Cl.[NH2:30][OH:31].C(=O)([O-])O.[Na+].[NH4+].[Cl-]>C(O)C.O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[C:25]([F:28])([F:27])[F:26])[CH2:9]/[C:10](/[C:12]2[CH:17]=[CH:16][N:15]=[C:14]([CH3:18])[CH:13]=2)=[N:30]\[OH:31])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 443297Hydroxyamine hydrochlorideHCID 516892Sodium BicarbonateHCID 66666136HCID 66666136, compound

Product 1

HCID 136167025HCID 136167025, compoundYield 79%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 3-(4-bromo-phenyl)-1-(2-methyl-pyridin-4-yl)-3-(2-trifluoromethyl-phenyl)-propan-1-one (80 mg), hydroxylamine hydrochloride (37 mg) and sodium hydrogencarbonate (45 mg) in a mixture of ethanol (4 mL) and water (0.7 mL) was heated under reflux for 2 hours. A saturated solution of NH4Cl was added, the phases were separated and the inorganic one was extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was dissolved in DME (5 mL) and HCl in dioxane (4M, 0.45 mL) were added at rt. The reaction mixture was stirred at 50° C. overnight, was concentrated and dissolved in ethyl acetate (5 mL) and a saturated aqueous solution of NaHCO3 (0.1 mL). A saturated aqueous solution of NH4Cl was added, the phases were separated and the inorganic one was extracted with EtOAc (2×). The combined organic phases were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel (CH2Cl2/MeOH 95:5) to yield the title compound (65 mg, 79%) as a white foam, MS (ESI+): m/z=463.1 ([M+H]+, 1Br).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 2 hours
  3. customthe phases were separated
  4. extractionthe inorganic one was extracted with EtOAc (2×)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. dissolutionThe crude product was dissolved in DME (5 mL)
  10. additionHCl in dioxane (4M, 0.45 mL) were added at rt
  11. concentrationwas concentrated
  12. dissolutiondissolved in ethyl acetate (5 mL)
  13. additionA saturated aqueous solution of NH4Cl was added
  14. customthe phases were separated
  15. extractionthe inorganic one was extracted with EtOAc (2×)
  16. washThe combined organic phases were washed with brine
  17. dry with materialdried over Na2SO4
  18. filtrationfiltered
  19. concentrationconcentrated in vacuo
  20. customThe crude product was purified by flash chromatography on silica gel (CH2Cl2/MeOH 95:5)

Sources & evidence

ORD record
ord-1f88040940474f2084a96997691c0f90
Source dataset
uspto-grants-2014_07
Patent number
US08765730B2

Reaction notes

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