Dicyclohexylcarbodiimide → HCID 70043676, compound

HRID 487425Notes

Reaction equation

HRID 487425 reaction equation
[ClH:1].[CH2:2]([O:9][C:10]([CH2:12][C@@H:13]1[NH:18][CH2:17][CH2:16][N:15]([CH2:19][C:20](O)=[O:21])[C:14]1=[O:23])=[O:11])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(=O)([O-])O.[Na+].O[N:30]1C(=O)CCC1=O.C1(N=C=NC2CCCCC2)CCCCC1>O1CCOCC1.O.Cl.O1CCOCC1>[ClH:1].[CH2:2]([O:9][C:10](=[O:11])[CH2:12][C@@H:13]1[NH:18][CH2:17][CH2:16][N:15]([CH2:19][C:20](=[O:21])[NH2:30])[C:14]1=[O:23])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

8

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 80170N-HydroxysuccinimideHCID 516892Sodium BicarbonateHCID 70046324HCID 70046324, compound

Product 1

HCID 70043676HCID 70043676, compoundYield 26.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent2×HCID 204431481,4-Dioxane hydrochlorideSolvent

Procedure

(S)-3-Benzyloxycarbonylmethyl-2-oxopiperazine-1-acetic acid hydrochloride (7.5 g) and sodium hydrogencarbonate (4.2 g) were dissolved in a mixture of 50 ml of dioxane and 50 ml of water. To the solution was added at 0° C. 5.5 g of di-t-butyl bicarbonate, and the mixture was stirred vigorously for one hour. The reaction mixture was concentrated to half of its original volume, and washed with ether then there was added 30 ml of a 10% aqueous solution of potassium hydrogen sulfate, followed by extraction with methylene chloride. The extract solution was dried over anhydrous magnesium sulfate, which was then concentrated to give a crude product. The crude product was dissolved in 50 ml of dioxane. To the solution was added 2.6 g of N-hydroxysuccinimide, then 5.2 g of dicyclohexylcarbodiimide. The mixture was stirred for one hour at room temperature. Insolubles were filtered off. To the filtrate was added 10 ml of 25% aqueous ammonia, and the mixture was stirred vigorously for one hour. The reaction mixture was concentrated under reduced pressure. The concentrate was dissolved in methylene chloride, and the solution was washed with water. The methylene chloride layer was dried over anhydrous magnesium sulfate, then concentrated under reduced pressure to give an oily product. The oily product was dissolved in 2N HCl-dioxane, and the solution was stirred for one hour. The reaction mixture was subjected to evaporation to dryness to give a crude product, which was recrystallized from ethanol to afford 2.0 g of the title compound as colorless prisms, m.p. 201°-202° C.

Workup

  1. additionTo the solution was added at 0° C
  2. concentrationThe reaction mixture was concentrated to half of its original volume
  3. washwashed with ether
  4. additionthere was added 30 ml of a 10% aqueous solution of potassium hydrogen sulfate
  5. extractionfollowed by extraction with methylene chloride
  6. dry with materialThe extract solution was dried over anhydrous magnesium sulfate, which
  7. concentrationwas then concentrated
  8. customto give a crude product
  9. filtrationInsolubles were filtered off
  10. additionTo the filtrate was added 10 ml of 25% aqueous ammonia
  11. stirringthe mixture was stirred vigorously for one hour
  12. concentrationThe reaction mixture was concentrated under reduced pressure
  13. dissolutionThe concentrate was dissolved in methylene chloride
  14. washthe solution was washed with water
  15. dry with materialThe methylene chloride layer was dried over anhydrous magnesium sulfate
  16. concentrationconcentrated under reduced pressure
  17. customto give an oily product
  18. stirringthe solution was stirred for one hour
  19. customThe reaction mixture was subjected to evaporation to dryness
  20. customto give a crude product, which
  21. customwas recrystallized from ethanol

Sources & evidence

ORD record
ord-bd38fd0a99984858a4e611ba6cc3d0f6
Source dataset
uspto-grants-1994_03
Patent number
US05294713

Reaction notes

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