Dicyclohexylcarbodiimide → HCID 53851693, compound

HRID 1982502Notes

Reaction equation

HRID 1982502 reaction equation
C1(N=C=NC2CCCCC2)CCCCC1.O.[C:17]([O:21][C:22]([NH:24][C@H:25]([C:30]([OH:32])=O)[CH2:26][CH:27]([CH3:29])[CH3:28])=[O:23])([CH3:20])([CH3:19])[CH3:18].ON1C(=O)CCC1=O.[CH3:41][O:42][C:43]1[C:48]([O:49][CH3:50])=[C:47]([O:51][CH3:52])[CH:46]=[CH:45][C:44]=1[CH2:53][N:54]1[CH2:59][CH2:58][NH:57][CH2:56][CH2:55]1.C1(N)C(F)=C(F)C(F)=C(N)C=1F.Cl.Cl>C(N(CC)CC)C.C(Cl)Cl>[CH3:29][CH:27]([CH3:28])[CH2:26][C@H:25]([NH:24][C:22](=[O:23])[O:21][C:17]([CH3:18])([CH3:19])[CH3:20])[C:30]([N:57]1[CH2:56][CH2:55][N:54]([CH2:53][C:44]2[CH:45]=[CH:46][C:47]([O:51][CH3:52])=[C:48]([O:49][CH3:50])[C:43]=2[O:42][CH3:41])[CH2:59][CH2:58]1)=[O:32]

Participants

8

Reactant 5

HCID 10868DicyclohexylcarbodiimideHCID 21109TrimetazidineHCID 80170N-HydroxysuccinimideHCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 12373896N-Boc-L-Leucine Hydrate

Product 1

HCID 53851693HCID 53851693, compoundYield 99%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

Under cooling with ice, a methylene chloride solution (30 ml) of N,N'-dicyclohexylcarbodiimide (41.2 g) was added dropwise to a methylene chloride solution (70 ml) containing tert-butoxycarbonyl-L-leucine monohydrate (4.98 g) and N-hydroxy succinimide (2.30 g), and the mixture was stirred at room temperature for 4 hours. While cooling again with ice, 1-(2,3,4-trimethoxyphenylmethyl)piperazine=dihydrochloride (6.79 g) was added, and triethylamine (8.5 ml) was then added dropwise. The mixture was stirred overnight at room temperature. After removal of methylene chloride by distillation under reduced pressure, ethyl acetate was added to the residue, and any insoluble matters were removed by filtration. The filtrate was washed first with an aqueous sodium bicarbonate solution and then with an aqueous saturated sodium chloride solution, dried over sodium sulfate and distilled under reduced pressure to remove the solvent, whereupon a crude reaction mixture was obtained as an oily viscous substance. This substance was purified by silica gel column chromatography (developing solvent:chloroform:methanol=20:1) to yield 9.5 g of tert-butyl (s)-3-methyl-1-[4-(2,3,4-trimethoxyphenylmethyl)-piperazine-1-yl carbonyl]butylcarbamate as a colorless oily viscous substance (yield: 99%).

Workup

  1. temperatureUnder cooling with ice
  2. additionwas added
  3. stirringThe mixture was stirred overnight at room temperature
  4. customAfter removal of methylene chloride
  5. distillationby distillation under reduced pressure, ethyl acetate
  6. additionwas added to the residue
  7. customany insoluble matters were removed by filtration
  8. washThe filtrate was washed first with an aqueous sodium bicarbonate solution
  9. dry with materialwith an aqueous saturated sodium chloride solution, dried over sodium sulfate
  10. distillationdistilled under reduced pressure
  11. customto remove the solvent
  12. customwhereupon a crude reaction mixture
  13. customwas obtained as an oily viscous substance
  14. customThis substance was purified by silica gel column chromatography (developing solvent:chloroform:methanol=20:1)

Sources & evidence

ORD record
ord-f407851b83b949c2bb8b9b6fbd3b8a56
Source dataset
uspto-grants-1986_06
Patent number
US04596803

Reaction notes

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