4'-Hydroxyacetophenone → Phenol, 4-(5-isoxazolyl)- (9CI)

HRID 1798810Notes

Reaction equation

HRID 1798810 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][CH:3]=1.CO[CH:13](OC)[N:14](C)C>>[O:10]1[C:8]([C:5]2[CH:6]=[CH:7][C:2]([OH:1])=[CH:3][CH:4]=2)=[CH:9][CH:13]=[N:14]1

Participants

3

Reactant 2

HCID 74694'-HydroxyacetophenoneHCID 78373Dimethylformamide dimethyl acetal

Product 1

HCID 135744209Phenol, 4-(5-isoxazolyl)- (9CI)

Procedure

1-(4-hydroxyphenyl)ethanone (5 g, 36.7 mmol) was heated in dimethylformamide dimethyl acetal (6.56 g, 55 mmol) at 100° C. overnight. The solution turned dark red. Volatile solvent was removed under high vacuum. The crude 3-(dimethylamino)-1-(4-hydroxyphenyl)prop-2-en-1-one was dissolved in ethanol, followed by addition of hydroxylamine hydrochloride salt. The mixture was heated under reflux for 3 hours. The solvent was removed under vacuum. The residue was purified twice by column chromatography through 120 g biotage silica gel cartridges eluting with 10-40% EtOAc/hexanes (gradient) and 20% ethyl acetate/hexanes (isocratic) to give the product as white solid. LRMS calc: 161.1; obs: 162.2 (M+1).

Workup

  1. customVolatile solvent was removed under high vacuum
  2. dissolutionThe crude 3-(dimethylamino)-1-(4-hydroxyphenyl)prop-2-en-1-one was dissolved in ethanol
  3. additionfollowed by addition of hydroxylamine hydrochloride salt
  4. temperatureThe mixture was heated
  5. temperatureunder reflux for 3 hours
  6. customThe solvent was removed under vacuum
  7. customThe residue was purified twice by column chromatography through 120 g biotage silica gel cartridges
  8. washeluting with 10-40% EtOAc/hexanes (gradient) and 20% ethyl acetate/hexanes (isocratic)

Sources & evidence

ORD record
ord-c4edbfe3e8144968af6806372f65b891
Source dataset
uspto-grants-2013_01
Patent number
US08343990B2

Reaction notes

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