Hydroxylamine → HCID 22459610, compound

HRID 2185099Notes

Reaction equation

HRID 2185099 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:14][C:15](SC)=[CH:16][C:17]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:18])[CH:6]=[CH:7][C:8]=1[C:9]1[O:13][CH:12]=[N:11][CH:10]=1.[NH2:27]O>C(O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:14][C:15]2[CH:16]=[C:17]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[O:18][N:27]=2)[CH:6]=[CH:7][C:8]=1[C:9]1[O:13][CH:12]=[N:11][CH:10]=1

Participants

4

Reactant 2

HCID 787HydroxylamineHCID 69695791HCID 69695791, compound

Product 1

HCID 22459610HCID 22459610, compoundYield 0%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To an oven dry flask was added acetophenone (0.4 mL, 3.33 mmol) followed by 10 mL of anhydrous DMF. The flask was cooled to 0° C. and to it was added sodium hydride (0.084 g, 3.33 mmol) over a 10 min. The flask was stirred at RT for 10 min. 1E (0.772 g, 3.33 mmol) was added over a 10 min. period and the reaction mixture was stirred at RT for 1 hour. Iodomethane (0.2 mL, 3.33 mmol) was added and the reaction mixture was stirred at RT for an additional hour, concentrated under reduced pressure and partitioned between ethyl acetate and water. The ethyl acetate layer was dried over sodium sulfate and concentrated under reduced pressure to yield 3-[[3-Methoxy-4-(5-oxazolyl)phenyl]amino]-3-(methylthio)-1-phenyl-2-propen-1-one (1.3 g), which was used for the subsequent step without further purification. To a solution of 3-[[3-Methoxy-4-(5-oxazolyl)phenyl]amino]-3-(methylthio)-1-phenyl-2-propen-1-one (1.2 g, 3.32 mmol) in 10 mL of ethanol was added hydroxylamine (50% solution in water, 0.3 mL, 4.98 mmol) and the contents refluxed for 4 hours. The reaction mixture was partitioned between ethyl acetate and water. The ethyl acetate layer was left at RT overnight and the solid that separates out (700 mgs) was filtered. 100 mgs of this solid was purified using preparative HPLC (YMC S5 ODS 30×250 mm Ballistic. Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA). The fraction having a retention time of 4.61 min. was collected, concentrated under reduced pressure, neutralized with 10% aqueous sodium carbonate and extracted into ethyl acetate. The ethyl acetate layer was concentrated to yield 0.015 mgs of the title compound. m.p. 173-175° C. (LC/MS retention time=4.61 min.; M+=334.22 Column: YMC S5 ODS 4.6×5.0 mm Ballistic. Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA).

Workup

  1. customwas used for the subsequent step without further purification
  2. temperaturethe contents refluxed for 4 hours
  3. customThe reaction mixture was partitioned between ethyl acetate and water
  4. filtrationthe solid that separates out (700 mgs) was filtered
  5. custom100 mgs of this solid was purified
  6. customwas collected
  7. concentrationconcentrated under reduced pressure
  8. extractionextracted into ethyl acetate
  9. concentrationThe ethyl acetate layer was concentrated

Sources & evidence

ORD record
ord-922223d17d3f4683bfd94d04cf0e0b85
Source dataset
uspto-grants-2002_06
Patent number
US06399773B1

Reaction notes

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