Diethyl Oxalate → HCID 53804563, compound

HRID 322991Notes

Reaction equation

HRID 322991 reaction equation
[C:1]([C:4]1[CH:25]=[CH:24][C:23]([O:26][CH2:27][C:28]2[CH:32]=[CH:31][S:30][CH:29]=2)=[CH:22][C:5]=1[O:6][CH:7]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[CH3:21])[CH2:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])(=O)[CH3:2].[C:33]([O:40]CC)(=O)[C:34]([O:36][CH2:37][CH3:38])=[O:35].[H-].[Na+].Cl.[NH2:46]O>C1(C)C=CC=CC=1.C(O)C.C(O)(=O)C>[CH2:37]([O:36][C:34]([C:33]1[O:40][N:46]=[C:1]([C:4]2[CH:25]=[CH:24][C:23]([O:26][CH2:27][C:28]3[CH:32]=[CH:31][S:30][CH:29]=3)=[CH:22][C:5]=2[O:6][CH:7]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[CH3:21])[CH2:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH:2]=1)=[O:35])[CH3:38]

Participants

8

Reactant 4

HCID 7268Diethyl OxalateHCID 24758Sodium hydrideHCID 443297Hydroxyamine hydrochlorideHCID 10503817HCID 10503817, compound

Product 1

HCID 53804563HCID 53804563, compoundYield 72.4%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

A solution of ethyl (RS)-4-[2-acetyl-5-(3-thienylmethoxy)phenoxy]-4-(2-methylphenyl)butanoate (2.91 g) and diethyl oxalate (2.82 g) in dry toluene are stirred at room temperature whilst adding sodium hydride (0.28 g, 60% dispersion in mineral oil) portionwise. The reaction mixture is heated at reflux for 5 hours then left at room temperature for 18 hours. Evaporation gives an orange oil which is dissolved in ethanol (100 mL) and treated with glacial acetic acid (1.5 mL). Hydroxylamine hydrochloride (0.49 g) is added and the mixture heated at reflux for 5 hours. The reaction mixture is partitioned between ethyl acetate (100 mL) and water (100 mL). The aqueous phase is extracted with three times ethyl acetate (50 mL). The combined organic phases are washed with brine (50 mL), with water (50 mL), dried over magnesium sulphate and evaporated. The residue is purified by flash chromatography on silica eluting with a mixture of ethyl acetate and pentane (1:1 v/v). Fractions homogeneous in the required product are combined and evaporated to give ethyl (RS)-4-[2-(5-ethoxycarbonylisoxazol-3-yl)-5-(3-thienylmethoxy)phenoxy]-4-(2-methylphenyl)butanoate (2.56 g) as an orange oil.

Workup

  1. temperatureThe reaction mixture is heated
  2. temperatureat reflux for 5 hours
  3. customEvaporation
  4. customgives an orange oil which
  5. temperaturethe mixture heated
  6. temperatureat reflux for 5 hours
  7. customThe reaction mixture is partitioned between ethyl acetate (100 mL) and water (100 mL)
  8. extractionThe aqueous phase is extracted with three times ethyl acetate (50 mL)
  9. washThe combined organic phases are washed with brine (50 mL), with water (50 mL)
  10. dry with materialdried over magnesium sulphate
  11. customevaporated
  12. customThe residue is purified by flash chromatography on silica eluting with a mixture of ethyl acetate and pentane (1:1 v/v)
  13. customevaporated

Sources & evidence

ORD record
ord-7e10ee824b8b4cb9a88db812a14b7eda
Source dataset
uspto-grants-2001_04
Patent number
US06211234B1

Reaction notes

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