3,5-Dimethyl-4-[2-(methyloxy)-5-nitrophenyl]isoxazole → Ethyl 7-(3,5-dimethyl-4-isoxazolyl)-4-hydroxy-6-(methyloxy)-3-quinolinecarboxylate

HRID 81975Notes

Reaction equation

HRID 81975 reaction equation
[CH2:1]([O:3][C:4](=[O:28])[C:5](=[CH:11][NH:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([C:21]2[C:22]([CH3:27])=[N:23][O:24][C:25]=2[CH3:26])[CH:14]=1)[C:6]([O:8]CC)=O)[CH3:2].CC1C(C2C=C([N+]([O-])=O)C=CC=2OC)=C(C)ON=1>C1(OC2C=CC=CC=2)C=CC=CC=1>[CH3:27][C:22]1[C:21]([C:15]2[CH:14]=[C:13]3[C:18]([C:6]([OH:8])=[C:5]([C:4]([O:3][CH2:1][CH3:2])=[O:28])[CH:11]=[N:12]3)=[CH:17][C:16]=2[O:19][CH3:20])=[C:25]([CH3:26])[O:24][N:23]=1

Participants

4

Reactant 2

HCID 574655703,5-Dimethyl-4-[2-(methyloxy)-5-nitrophenyl]isoxazoleHCID 57465590HCID 57465590, compound

Product 1

HCID 178469491Ethyl 7-(3,5-dimethyl-4-isoxazolyl)-4-hydroxy-6-(methyloxy)-3-quinolinecarboxylateYield 92%

Reagents, catalysts & solvents 1

HCID 7583Diphenyl EtherSolvent

Procedure

Diethyl({[3-(3,5-dimethyl-4-isoxazolyl)-4-(methyloxy)phenyl]amino}methylidene)propanedioate (for a preparation see Intermediate 3) (35 g, 90 mmol) was added in small portions over 10 min to boiling diphenyl ether (500 ml)—vigorous effervescence results. The mixture was heated at reflux for 20 min, the heater was switched off and removed from the vessel and the solution allowed to cool in air over 2 h to 40° C., giving some precipitation of a brown granular solid. The mixture was diluted with ether (300 ml) and allowed to stand overnight, then filtered and the solid washed with ether (2×200 ml) and dried to give ethyl 7-(3,5-dimethyl-4-isoxazolyl)-4-hydroxy-6-(methyloxy)-3-quinolinecarboxylate (28.4 g, 83 mmol, 92% yield). LCMS (formate) Rt 0.73 min, MH+ 343

Workup

  1. additionwas added in small portions over 10 min
  2. customresults
  3. temperatureThe mixture was heated
  4. temperatureat reflux for 20 min
  5. customremoved from the vessel
  6. temperatureto cool in air over 2 h to 40° C.
  7. customgiving
  8. customsome precipitation of a brown granular solid
  9. additionThe mixture was diluted with ether (300 ml)
  10. filtrationfiltered
  11. washthe solid washed with ether (2×200 ml)
  12. customdried

Sources & evidence

ORD record
ord-488994e7ea97457c8019a4ab92ce5b44
Source dataset
uspto-grants-2014_09
Patent number
US08846709B2

Reaction notes

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