Hydroxylamine HCl → HCID 135971234, compound

HRID 2041994Notes

Reaction equation

HRID 2041994 reaction equation
[C:1]([C:5]1[CH:25]=[CH:24][CH:23]=[CH:22][C:6]=1[O:7][CH:8]1[CH2:11][N:10]([C:12]([C:14]2[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=2)=[O:13])[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[Cl-].O[NH3+].[C:29](=[O:32])([O-])[OH:30].[Na+].C(N1C=CN=C1)([N:36]1C=CN=C1)=O.N12CCCN=C1CCCCC2.O.Cl>CS(C)=O.C1COCC1>[C:1]([C:5]1[CH:25]=[CH:24][CH:23]=[CH:22][C:6]=1[O:7][CH:8]1[CH2:11][N:10]([C:12]([C:14]2[CH:15]=[CH:16][C:17]([C:18]3[NH:36][C:29](=[O:32])[O:30][N:19]=3)=[CH:20][CH:21]=2)=[O:13])[CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

9

Reactant 6

HCID 21645Hydroxylamine HClHCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 516892Sodium BicarbonateHCID 21885828Hydrate;hydrochlorideHCID 59577237HCID 59577237, compound

Product 1

HCID 135971234HCID 135971234, compoundYield 59.3%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 4-{[3-(2-tert-butylphenoxy)azetidin-1-yl]carbonyl}benzonitrile (2.00 g, 6.00 mmol) in DMSO (5.0 mL) was added hydroxylammonium chloride (2.08 g, 30.0 mmol) and sodium hydrogen carbonate (2.52 g, 30.0 mmol) at 90° C. After 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 (10.0 mL), added to a stirred solution of 1,1′-carbonylbis-1H-imidazole (1.07 g, 6.6 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (1.07 g, 6.6 mmol) in THF (10.0 mL) and the resulting reaction mixture was stirred at room temperature for 2 h. Then, the reaction mixture was poured into 1N HCl water solution (150.0 mL) and extracted with ethyl acetate (2×100.0 ml). The combined organics were washed with water (2×150 mL), saturated sodium chloride (100 mL), dried (MgSO4), filtered, and concentrated under reduced pressure. The resulting mixture was washed with acetonitrile and diethyl ether to provide 3-(4-{[3-(2-tert-butylphenoxy)azetidin-1-yl]carbonyl}phenyl)-1,2,4-oxadiazol-5(4H)-one (1.40 g, 59%) as a colorless solid.

Workup

  1. customAfter 1 h the reaction mixture was partitioned between ethyl acetate and water
  2. customseparated
  3. washThe organic layer was washed with saturated sodium chloride
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe residue was dissolved in THF (10.0 mL)
  8. customthe resulting reaction mixture
  9. extractionextracted with ethyl acetate (2×100.0 ml)
  10. washThe combined organics were washed with water (2×150 mL), saturated sodium chloride (100 mL)
  11. dry with materialdried (MgSO4)
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. washThe resulting mixture was washed with acetonitrile and diethyl ether

Sources & evidence

ORD record
ord-442094a44385455fa7ba44dbd5f33179
Source dataset
uspto-grants-2013_11
Patent number
US08586571B2

Reaction notes

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