Ethylmorpholine → 2(R)-[1(S)-(tert-butoxycarbonyl)-4-phenylbutyl]-N-(4(S)-isopropyl-2,5-dioxo-1-imidazolidinyl)-4-methylvaleramide

HRID 651789Notes

Reaction equation

HRID 651789 reaction equation
[C:1]([O:5][C:6]([C@H:8]([C@@H:18]([CH2:23][CH:24]([CH3:26])[CH3:25])[C:19]([NH:21][NH2:22])=[O:20])[CH2:9][CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N:27]([C@@H:30]([CH:35]([CH3:37])[CH3:36])[C:31](OC)=[O:32])=[C:28]=[O:29].C(N1CCOCC1)C>ClCCl>[C:1]([O:5][C:6]([C@H:8]([C@@H:18]([CH2:23][CH:24]([CH3:26])[CH3:25])[C:19]([NH:21][N:22]1[C:31](=[O:32])[C@H:30]([CH:35]([CH3:37])[CH3:36])[NH:27][C:28]1=[O:29])=[O:20])[CH2:9][CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 7525EthylmorpholineHCID 10397066Methyl (S)-(-)-2-Isocyanato-3-methylbutyrateHCID 702001082(R)-[1(S)-(tert-butoxycarbonyl)-4-phenylbutyl]-4-methylvalerohydrazide

Product 1

HCID 702395592(R)-[1(S)-(tert-butoxycarbonyl)-4-phenylbutyl]-N-(4(S)-isopropyl-2,5-dioxo-1-imidazolidinyl)-4-methylvaleramideYield 67.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 0.517 g of 2(R)-[1(S)-(tert-butoxycarbonyl)-4-phenylbutyl]-4-methylvalerohydrazide in 5 ml of dichloromethane was treated with 0.302 g of methyl (S)-(+)-2-isocyanato-3-methylbutyrate and 0.3 ml of N-ethylmorpholine. The mixture was stirred at room temperature for 4 hours and then the solution was washed with 5% aqueous citric acid solution, saturated sodium chloride solution, dried over anhydrous magnesium sulphate and evaporated. The residue was dissolved in 5 ml of toluene containing 0.2 ml of triethylamine. The mixture was heated at reflux for 24 hours. The solution was cooled, diluted with ethyl acetate and washed with 5% aqueous citric acid solution, saturated sodium chloride solution, dried over anhydrous magnesium sulphate, and evaporated. The residue was triturated with ether and there was obtained 0.468 g of 2(R)-[1(S)-(tert-butoxycarbonyl)-4-phenylbutyl]-N-(4(S)-isopropyl-2,5-dioxo-1-imidazolidinyl)-4-methylvaleramide in the form of a white solid.

Workup

  1. washthe solution was washed with 5% aqueous citric acid solution, saturated sodium chloride solution
  2. dry with materialdried over anhydrous magnesium sulphate
  3. customevaporated
  4. dissolutionThe residue was dissolved in 5 ml of toluene containing 0.2 ml of triethylamine
  5. temperatureThe mixture was heated
  6. temperatureat reflux for 24 hours
  7. temperatureThe solution was cooled
  8. additiondiluted with ethyl acetate
  9. washwashed with 5% aqueous citric acid solution, saturated sodium chloride solution
  10. dry with materialdried over anhydrous magnesium sulphate
  11. customevaporated
  12. customThe residue was triturated with ether

Sources & evidence

ORD record
ord-eda6b51d9b004683b7fc6f6a1a85fca4
Source dataset
uspto-grants-2001_08
Patent number
US06281363B1

Reaction notes

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