Ethyl 4-hydroxyisoxazole-3-carboxylate → 4-Hydroxy-N-[4-(4-piperidinomethyl-2-pyridyloxy)-cis-2-butenyl]isoxazole-3-carboxamide

HRID 52073Notes

Reaction equation

HRID 52073 reaction equation
[OH:1][C:2]1[C:3]([C:7]([O:9]CC)=O)=[N:4][O:5][CH:6]=1.[N:12]1([CH2:18][C:19]2[CH:24]=[CH:23][N:22]=[C:21]([O:25][CH2:26]/[CH:27]=[CH:28]\[CH2:29][NH2:30])[CH:20]=2)[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1>C1(C)C=CC=CC=1>[OH:1][C:2]1[C:3]([C:7]([NH:30][CH2:29]/[CH:28]=[CH:27]\[CH2:26][O:25][C:21]2[CH:20]=[C:19]([CH2:18][N:12]3[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]3)[CH:24]=[CH:23][N:22]=2)=[O:9])=[N:4][O:5][CH:6]=1

Participants

4

Reactant 2

HCID 13180537Ethyl 4-hydroxyisoxazole-3-carboxylateHCID 136724732-Buten-1-amine, 4-[[4-(1-piperidinylmethyl)-2-pyridinyl]oxy]-, (Z)-

Product 1

HCID 677262414-Hydroxy-N-[4-(4-piperidinomethyl-2-pyridyloxy)-cis-2-butenyl]isoxazole-3-carboxamideYield 31%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

375 mg of ethyl 4-hydroxy-3-isoxazolecarboxylate (prepared as described in Preparation 4) were added to a solution of 520 mg of 4-(4-piperidinomethyl-2-pyridyloxy) -cis-2-butenylamine in 10 ml of toluene, and the resulting mixture was heated under reflux for 6 hours. At the end of this time, the solvent was removed by distillation under reduced pressure, and the residue was dissolved in ethyl acetate. The resulting solution was washed with a saturated aqueous solution of sodium hydrogencarbonate and then with a saturated aqueous solution of sodium chloride, after which it was dried over anhydrous magnesium sulfate. The solvent was then removed by distillation under reduced pressure, and the residue was purified by column chromatography through silica gel, using a 1:19 by volume mixture of methanol and ethyl acetate as the eluent, to give 228 mg (yield 31%) of the title compound as an oil.

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureunder reflux for 6 hours
  3. customAt the end of this time, the solvent was removed by distillation under reduced pressure
  4. dissolutionthe residue was dissolved in ethyl acetate
  5. washThe resulting solution was washed with a saturated aqueous solution of sodium hydrogencarbonate
  6. dry with materialwith a saturated aqueous solution of sodium chloride, after which it was dried over anhydrous magnesium sulfate
  7. customThe solvent was then removed by distillation under reduced pressure
  8. customthe residue was purified by column chromatography through silica gel
  9. additionby volume mixture of methanol and ethyl acetate as the eluent

Sources & evidence

ORD record
ord-608f15cf0b2546d6b7add48b68af1c23
Source dataset
uspto-grants-1997_04
Patent number
US05616579

Reaction notes

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