Diethyl Oxalate → Ethyl 3-[2,4-bis(benzyloxy)-6-(4-nitrophenoxy)phenyl]-5-hydroxy-4,5-dihydroisoxazole-5-carboxylate

HRID 880368Notes

Reaction equation

HRID 880368 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:12]=[C:11]([O:23][C:24]2[CH:29]=[CH:28][C:27]([N+:30]([O-:32])=[O:31])=[CH:26][CH:25]=2)[C:10]=1[C:33](=[N:35][OH:36])[CH3:34])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.CCCCCC.[C:48](OCC)(=[O:54])[C:49]([O:51][CH2:52][CH3:53])=[O:50].[NH4+].[Cl-]>C1COCC1>[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:12]=[C:11]([O:23][C:24]2[CH:25]=[CH:26][C:27]([N+:30]([O-:32])=[O:31])=[CH:28][CH:29]=2)[C:10]=1[C:33]1[CH2:34][C:48]([OH:54])([C:49]([O:51][CH2:52][CH3:53])=[O:50])[O:36][N:35]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 7268Diethyl OxalateHCID 8058HexaneHCID 25517Ammonium ChlorideHCID 866623761-[2,4-Bis(benzyloxy)-6-(4-nitrophenoxy)phenyl]-N-hydroxyethanimineHCID 178418339Butyllithium

Product 1

HCID 66758807Ethyl 3-[2,4-bis(benzyloxy)-6-(4-nitrophenoxy)phenyl]-5-hydroxy-4,5-dihydroisoxazole-5-carboxylateYield 21%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 1-[2,4-bis(benzyloxy)-6-(4-nitrophenoxy)phenyl]-N-hydroxyethanimine (10 g, 44 mmol) was added drop wise 2 M n-ButLi in hexane (45 mL, 44 mmol) at −78° C. and the stirring was continued for 1 hour at −78° C. then for ½ hour at room temperature. After recooling at −78° C., a solution of diethyl oxalate (3.22 g, 22 mmol) in THF (50 mL) was cannuled into the cloudy solution. The mixture was warmed at rt over 16 hours before the addition of a NH4Cl saturated solution (100 mL). The organic and aqueous layers were separated and the latter was diluted with ethyl acetate and thoroughly washed with brine. After drying over Na2SO4, the solvent was removed and the residue was chromatographed on silica gel eluting with ethyl acetate/hexane 7/5, to provide the title compound (2.7 g, yield 17%).

Workup

  1. waitfor ½ hour at room temperature
  2. customAfter recooling at −78° C.
  3. customThe organic and aqueous layers were separated
  4. additionthe latter was diluted with ethyl acetate
  5. washthoroughly washed with brine
  6. dry with materialAfter drying over Na2SO4
  7. customthe solvent was removed
  8. customthe residue was chromatographed on silica gel eluting with ethyl acetate/hexane 7/5

Sources & evidence

ORD record
ord-6a55c9a157f241ff972e56b75bf76c46
Source dataset
uspto-grants-2015_03
Patent number
US08993556B2

Reaction notes

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