Hydrochloric Acid → Ethyl 5-[2,4-bis(methoxymethoxy)-6-(4-nitrophenoxy)phenyl]isoxazole-3-carboxylate

HRID 880360Notes

Reaction equation

HRID 880360 reaction equation
[CH3:1][O:2][CH2:3][O:4][C:5]1[CH:10]=[C:9]([O:11][CH2:12][O:13][CH3:14])[CH:8]=[C:7]([O:15][C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=2)[C:6]=1[C:25](=[O:34])[CH2:26][C:27](=O)[C:28]([O:30][CH2:31][CH3:32])=[O:29].CC(O[Na])=O.[NH2:40]O.Cl.Cl>C1COCC1.C(O)C.C(OCC)(=O)C>[CH3:1][O:2][CH2:3][O:4][C:5]1[CH:10]=[C:9]([O:11][CH2:12][O:13][CH3:14])[CH:8]=[C:7]([O:15][C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=2)[C:6]=1[C:25]1[O:34][N:40]=[C:27]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH:26]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 443297Hydroxyamine hydrochlorideHCID 66760003Ethyl 4-[2,4-bis(methoxymethoxy)-6-(4-nitrophenoxy)phenyl]-2,4-dioxobutanoateHCID 178418247HCID 178418247, compound

Product 1

HCID 66759150Ethyl 5-[2,4-bis(methoxymethoxy)-6-(4-nitrophenoxy)phenyl]isoxazole-3-carboxylateYield 49.5%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of ethyl 4-[2,4-bis(methoxymethoxy)-6-(4-nitrophenoxy)phenyl]-2,4-dioxobutanoate (71 g, 149 mmol) in THF (250 mL) and ethanol (500 mL) is added CH3COONa (24.4 g, 298 mmol) and NH2OH.HCl (22.8 g, 328 mmol) at room temperature. After the conversion to the oximes is complete, 6 M HCl solution was added dropwise to reach pH 2 to promote the cyclization. After stirring for 24 hours, Na2HPO4 was added to reach pH 6 and the suspension taken up in ethyl acetate was thoroughly washed with brine and dried over Na2SO4. The solvent was removed and the residue was crystallized from a mixture of MTBE (240 mL) and hexane (180 mL), to provide the title compound (35 g, 49% yield).

Workup

  1. washwas thoroughly washed with brine
  2. dry with materialdried over Na2SO4
  3. customThe solvent was removed
  4. customthe residue was crystallized from a mixture of MTBE (240 mL) and hexane (180 mL)

Sources & evidence

ORD record
ord-b23df8484d3c4203b72f2f63c9010ac7
Source dataset
uspto-grants-2015_03
Patent number
US08993556B2

Reaction notes

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