Ethyl Acetate → HCID 131712871, compound

HRID 2198662Notes

Reaction equation

HRID 2198662 reaction equation
[NH:1]([C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])[C@H:2]([C:7]([OH:9])=O)[C@H:3]([CH2:5][CH3:6])[CH3:4].C1C2C3C(=O)N(O)[C:27](=[O:28])[CH:26]3C1C=C2.C1CCC([N:39]=C=NC2CCCCC2)CC1.[C:48]([O:51]CC)(=[O:50])[CH3:49]>O1CCOCC1>[NH:1]([C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])[C@H:2]([C:7]([NH:39][C@H:49]([C:48]([OH:51])=[O:50])[C@@H:27]([CH3:26])[OH:28])=[O:9])[C@H:3]([CH2:5][CH3:6])[CH3:4]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 10868DicyclohexylcarbodiimideHCID 895293a,4,7,7a-Tetrahydro-2-hydroxy-4,7-methano-1H-isoindole-1,3(2H)-dioneHCID 2724772N-[(Phenylmethoxy)carbonyl]-L-isoleucine

Product 1

HCID 131712871HCID 131712871, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

In 500 ml of a mixed solvent of dioxane and ethyl acetate (1:1) were dissolved 24.3 g of Z-Ile-OH and 19.8 g of HONB. The solution was cooled with ice, followed by adding 20.8 g of DCC. The mixture was stirred for two hours. The precipitating DCU was removed by filtration, then the solvent was removed by distillation. The residue was crystallized from petroleum benzine. The crystals were recovered by filtration and dissolved in 200 ml of DMF. Separately 18 g of Thr and 12.8 ml of TEA were dissolved in a mixed solvent consisting of 200 ml of water and 50 ml of DMF. The solution was cooled with ice, and then the previously prepared DMF solution of activated ester was added. The mixture was stirred for one hour, and further stirred for 14 hours at a room temperature. Insolubles were removed by filtration, then the solvent was evaporated off. The residue was dissolved in 300 ml of 5% aqueous solution of sodium hydrogen-carbonate, and the solution was washed with diethyl ether. The aqueous layer was separated and acidified with 1N-hydrochloric acid, followed by two extractions, each with a 200 ml portion of AcOEt. The extracts were combined and washed with water, followed by drying over anhydrous sodium sulfate. The solvent was then evaporated off. To the residue was then added AcOEt-diethyl ether, and the resulting crystals were recovered by filtration. Yield 24.4 g (72.8%); m.p. 160°-162° C.; [α]D24 -10.3° (c=0.57, MeOH); Rf1 =0.36

Workup

  1. temperatureThe solution was cooled with ice
  2. customThe precipitating DCU was removed by filtration
  3. customthe solvent was removed by distillation
  4. customThe residue was crystallized from petroleum benzine
  5. filtrationThe crystals were recovered by filtration
  6. dissolutiondissolved in 200 ml of DMF
  7. dissolutionSeparately 18 g of Thr and 12.8 ml of TEA were dissolved in a mixed solvent
  8. temperatureThe solution was cooled with ice
  9. additionthe previously prepared DMF solution of activated ester was added
  10. stirringThe mixture was stirred for one hour
  11. stirringfurther stirred for 14 hours at a room temperature
  12. customInsolubles were removed by filtration
  13. customthe solvent was evaporated off
  14. dissolutionThe residue was dissolved in 300 ml of 5% aqueous solution of sodium hydrogen-carbonate
  15. washthe solution was washed with diethyl ether
  16. customThe aqueous layer was separated
  17. extractionfollowed by two extractions
  18. washwashed with water
  19. dry with materialby drying over anhydrous sodium sulfate
  20. customThe solvent was then evaporated off
  21. filtrationadded AcOEt-diethyl ether, and the resulting crystals were recovered by filtration

Sources & evidence

ORD record
ord-c72dad53a8604d63a5f96f8b30d194d5
Source dataset
uspto-grants-1982_11
Patent number
US04358440

Reaction notes

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