Hydroxylamine HCl → HCID 136340683, compound

HRID 534885Notes

Reaction equation

HRID 534885 reaction equation
[Cl-].O[NH3+:3].[C:4]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[N:14]1[CH2:19][CH2:18][N:17]([C:20]([C:22]2[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[CH:24][CH:23]=2)=[O:21])[CH2:16][CH2:15]1)([CH3:7])([CH3:6])[CH3:5].[C:30](=[O:33])([O-])[OH:31].[Na+].O.Cl>CS(C)=O>[C:4]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[N:14]1[CH2:15][CH2:16][N:17]([C:20]([C:22]2[CH:23]=[CH:24][C:25]([C:26]3[NH:3][C:30](=[O:33])[O:31][N:27]=3)=[CH:28][CH:29]=2)=[O:21])[CH2:18][CH2:19]1)([CH3:7])([CH3:5])[CH3:6]

Participants

6

Reactant 4

HCID 21645Hydroxylamine HClHCID 516892Sodium BicarbonateHCID 21885828Hydrate;hydrochlorideHCID 66751327HCID 66751327, compound

Product 1

HCID 136340683HCID 136340683, compoundYield 78.5%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of hydroxylammonium chloride (1.04 g) in DMSO (10.0 mL) was stirred at 40° C. After stirred at 40° C. for 1 h, a mixture of 4-{[4-(2-tert-butylphenyl)piperazin-1-yl]carbonyl}benzonitrile obtained in Example 16 (1.1 g) and sodium hydrogen carbonate (1.26 g) was added to the mixture. After stirred at 90° C. for 1 h, the reaction mixture was partitioned between ethyl acetate and water and separated. The organic layer was washed with saturated sodium chloride, dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was dissolved in THF (30.0 mL), added to a mixture of 1,1′-carbonyl bis-1H-imidazole (0.568 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.522 mL) and the resulting reaction mixture was stirred at room temperature for 3 h. After this time, the reaction mixture was poured into 1 M HCl water solution and extracted with ethyl acetate. The combined organics were washed with saturated sodium chloride, dried (MgSO4), filtered, and concentrated under reduced pressure to provide the title compound (1.01 g, 78%) as a solid.

Workup

  1. stirringAfter stirred at 40° C. for 1 h
  2. additionwas added to the mixture
  3. stirringAfter stirred at 90° C. for 1 h
  4. customthe reaction mixture was partitioned between ethyl acetate and water
  5. customseparated
  6. washThe organic layer was washed with saturated sodium chloride
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. dissolutionThe residue was dissolved in THF (30.0 mL)
  11. additionadded to a mixture of 1,1′-carbonyl bis-1H-imidazole (0.568 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.522 mL)
  12. customthe resulting reaction mixture
  13. stirringwas stirred at room temperature for 3 h
  14. extractionextracted with ethyl acetate
  15. washThe combined organics were washed with saturated sodium chloride
  16. dry with materialdried (MgSO4)
  17. filtrationfiltered
  18. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-9f015e98e18b478cb46d60577e836aa7
Source dataset
uspto-grants-2014_10
Patent number
US08853215B2

Reaction notes

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