Dicyclohexylcarbodiimide → HCID 13455629, compound

HRID 2164873Notes

Reaction equation

HRID 2164873 reaction equation
O.[C:2]([O:6][C:7]([NH:9][C@H:10]([C:15]([OH:17])=O)[CH2:11][CH:12]([CH3:14])[CH3:13])=[O:8])([CH3:5])([CH3:4])[CH3:3].ON1C(=O)CCC1=O.C1(N=C=NC2CCCCC2)CCCCC1.[C:41]1([CH:47]([C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)[N:48]2[CH2:53][CH2:52][NH:51][CH2:50][CH2:49]2)[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1>C(Cl)Cl>[C:54]1([CH:47]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[N:48]2[CH2:49][CH2:50][N:51]([C:15]([C@@H:10]([NH:9][C:7](=[O:8])[O:6][C:2]([CH3:3])([CH3:4])[CH3:5])[CH2:11][CH:12]([CH3:13])[CH3:14])=[O:17])[CH2:52][CH2:53]2)[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=1

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 70048BenzhydrylpiperazineHCID 80170N-HydroxysuccinimideHCID 12373896N-Boc-L-Leucine Hydrate

Product 1

HCID 13455629HCID 13455629, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a methylene chloride solution (100 ml) containing tert-butoxycarbonyl-L-leucine monohydrate (9.96 g) and N-hydroxy succinimide (4.6 g) was added dropwise a methylene chloride solution (50 ml) of N,N'-dicyclohexylcarbodiimide (8.24 g) with a length of time for 1 hour under cooling with ice. After being stirred at room temperature for 4 hours, the reaction mixture was again cooled with ice, and a methylene chloride solution (50 ml) of 1-(diphenylmethyl)piperazine (10.08 g) was added dropwise in 20 minutes. The mixture was stirred overnight at room temperature. Following the removal of the precipitate by filtration, the solvent was removed by distillation under reduced pressure, and ethyl acetate was added. After any insoluble matters were again removed by filtration, the filtrate was washed first with an aqueous sodium bicarbonate solution and then with a saturated sodium chloride solution, dried over magnesium sulfate and distilled under reduced pressure to remove the solvent, whereupon a crude reaction mixture was obtained. This reaction mixture was purified by silica gel column chromatography (developing solvent: chloroform followed by chloroform:methanol=50:1) to yield 16.5 g of tert-butyl (s)-1-(4-diphenylmethylpiperazine-1-yl carbonyl)-3-methylbutylcarbamate as a colorless amorphous substance (yield: 89%).

Workup

  1. temperatureunder cooling with ice
  2. temperaturethe reaction mixture was again cooled with ice
  3. stirringThe mixture was stirred overnight at room temperature
  4. customthe removal of the precipitate
  5. filtrationby filtration
  6. customthe solvent was removed by distillation under reduced pressure, and ethyl acetate
  7. additionwas added
  8. customAfter any insoluble matters were again removed by filtration
  9. washthe filtrate was washed first with an aqueous sodium bicarbonate solution
  10. dry with materialwith a saturated sodium chloride solution, dried over magnesium sulfate
  11. distillationdistilled under reduced pressure
  12. customto remove the solvent
  13. customwhereupon a crude reaction mixture
  14. customwas obtained
  15. customThis reaction mixture was purified by silica gel column chromatography (developing solvent: chloroform followed by chloroform:methanol=50:1)

Sources & evidence

ORD record
ord-9dc8500581c44524884f83ed7b7bf27a
Source dataset
uspto-grants-1985_03
Patent number
US04507297

Reaction notes

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