N-Phthaloylglycine → 2-[(3-Ethyl-1,2,4-oxadiazol-5-yl)methyl]-1H-isoindole-1,3(2H)-dione

HRID 2352558Notes

Reaction equation

HRID 2352558 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.[C:13]1(=[O:27])[N:17]([CH2:18][C:19]([OH:21])=O)[C:16](=[O:22])[C:15]2=[CH:23][CH:24]=[CH:25][CH:26]=[C:14]12.[C:28](=[N:32]O)([NH2:31])[CH2:29][CH3:30]>C1COCC1>[CH2:29]([C:28]1[N:32]=[C:19]([CH2:18][N:17]2[C:13](=[O:27])[C:14]3=[CH:26][CH:25]=[CH:24][CH:23]=[C:15]3[C:16]2=[O:22])[O:21][N:31]=1)[CH3:30]

Participants

5

Reactant 3

HCID 20825N-PhthaloylglycineHCID 682631,1'-CarbonyldiimidazoleHCID 4092053N-Hydroxypropionimidamide

Product 1

HCID 140319642-[(3-Ethyl-1,2,4-oxadiazol-5-yl)methyl]-1H-isoindole-1,3(2H)-dione

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

At 40° C., a suspension of 26.0 g of carbonyldiimidazole in 250 ml of THF is added to a solution of 65.7 g of phthalimidoacetic acid in 500 ml of THF (absolute). After about one hour, no release of gas can be observed any longer. At this point in time, a solution of 28.2 g of propionamidoxime in 50 ml of THF is added, and the mixture is stirred at room temperature for 24 hours. After the precipitate has been filtered off, the filtrate is concentrated under vacuum and, after addition of 500 ml of dry xylene, is heated under reflux for 6 hours on a water trap. The still hot solution is separated from the oily residue and concentrated under vacuum. Crystallization from EtOH yields 31.5 g (76.5%, based on carbonyldiimidazole) of oxadiazole having a melting point of 106°-107° C.

Workup

  1. filtrationAfter the precipitate has been filtered off
  2. concentrationthe filtrate is concentrated under vacuum
  3. additionafter addition of 500 ml of dry xylene
  4. temperatureis heated
  5. temperatureunder reflux for 6 hours on a water trap
  6. customThe still hot solution is separated from the oily residue
  7. concentrationconcentrated under vacuum
  8. customCrystallization from EtOH
  9. customyields 31.5 g (76.5%, based on carbonyldiimidazole) of oxadiazole having a melting point of 106°-107° C.

Sources & evidence

ORD record
ord-b7c70a70a77b446099c122016caf5781
Source dataset
uspto-grants-1989_10
Patent number
US04877792

Reaction notes

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