Triethylamine → N-(Nalpha-benzyloxycarbonyl-Nepsilon-tert-butoxycarbonyl-L-lysyl)-L-proline tert-butyl ester

HRID 1031811

Reaction equation

HRID 1031811 reaction equation
[C:1]([O:5][C:6](=[O:12])[C@@H:7]1[CH2:11][CH2:10][CH2:9][NH:8]1)([CH3:4])([CH3:3])[CH3:2].[CH2:13]([O:20][C:21]([NH:23][C@H:24]([C:37](O)=[O:38])[CH2:25][CH2:26][CH2:27][CH2:28][NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[O:22])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.P(C#N)(=O)(OCC)OCC.C(N(CC)CC)C>CN(C)C=O.O>[C:1]([O:5][C:6](=[O:12])[C@@H:7]1[CH2:11][CH2:10][CH2:9][N:8]1[C:37](=[O:38])[C@H:24]([CH2:25][CH2:26][CH2:27][CH2:28][NH:29][C:30]([O:32][C:33]([CH3:35])([CH3:34])[CH3:36])=[O:31])[NH:23][C:21]([O:20][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:22])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 76257Diethyl cyanophosphonateHCID 98765IN2-(benzyloxycarbonyl)-N6-(tert-butoxycarbonyl)-L-lysineHCID 6453108L-Proline 1,1-dimethylethyl ester

Product 1

HCID 14010667N-(Nalpha-benzyloxycarbonyl-Nepsilon-tert-butoxycarbonyl-L-lysyl)-L-proline tert-butyl esterYield 73.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

In 30 ml of N,N-dimethylformamide are dissolved 2.4 g of L-proline tert-butyl ester and 5.87 g of Nα -benzyloxycarbonyl-Nε -tert-butoxycarbonyl-L-lysine, and 3 g of diethyl phosphorocyanidate is added dropwise to the solution under ice-cooling. After stirring for 30 minutes, a solution of 1.42 g of triethylamine in 5 ml of N,N-dimethylformamide is added to the mixture, followed by stirring under ice-cooling for 1 hour and then at room temperature for 2 hours. 500 ml of water is added to the reaction mixture, and the mixture is extracted with 300 ml of ethyl acetate. The extract is washed with aqueous dilute phosphoric acid, 0.1N aqueous sodium hydroxide and water, successively, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting oily material is purified by silica gel column chromatography (hexane:ethyl acetate=2:1 to 1:1) to give 5.5 g of N-(Nα -benzyloxycarbonyl-Nε -tert-butoxycarbonyl-L-lysyl)-L-proline tert-butyl ester as a colorless oil.

Workup

  1. additionis added dropwise to the solution under ice-
  2. temperaturecooling
  3. stirringby stirring under ice-
  4. temperaturecooling for 1 hour
  5. waitat room temperature for 2 hours
  6. extractionthe mixture is extracted with 300 ml of ethyl acetate
  7. washThe extract is washed with aqueous dilute phosphoric acid, 0.1N aqueous sodium hydroxide and water
  8. dry with materialsuccessively, dried over anhydrous magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe resulting oily material is purified by silica gel column chromatography (hexane:ethyl acetate=2:1 to 1:1)

Sources & evidence

ORD record
ord-c9f50474bb534b5284b2b42befb7309b
Source dataset
uspto-grants-1990_09
Patent number
US04954625

Linked notes

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