Ethylmorpholine → HCID 86744638, compound

HRID 982571Notes

Reaction equation

HRID 982571 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:25]([OH:27])=O)[CH2:10][CH2:11][CH2:12][CH2:13][NH:14][C:15]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:16])=[O:7])([CH3:4])([CH3:3])[CH3:2].ClC(OCC(C)C)=O.C(N1CCOCC1)C.Cl.[CH2:45]([O:47][C:48](=[O:52])[C@H:49]([CH3:51])[NH2:50])[CH3:46]>O1CCCC1>[CH2:45]([O:47][C:48](=[O:52])[C@H:49]([CH3:51])[NH:50][C:25](=[O:27])[C@H:9]([CH2:10][CH2:11][CH2:12][CH2:13][NH:14][C:15]([O:17][CH2:18][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)=[O:16])[NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH3:46]

Participants

6

Reactant 4

HCID 7525Ethylmorpholine2×HCID 62365Isobutyl chloroformateHCID 2724356L-Alanine, ethyl ester, hydrochloride (1:1)HCID 2724765Boc-Lys(Z)-OH

Product 1

HCID 86744638HCID 86744638, compoundYield 77.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

13.3 g of Nα -tert.butoxycarbonyl-Nε -benzyloxycarbonyl-L-lysine were dissolved in 100 ml of tetrahydrofuran and the solution was cooled to -20° C. 4.58 ml of isobutyl chloroformate and 4.48 ml of N-ethylmorpholine were then added. After stirring at -20° C. for 2 minutes 5.37 g of L-alanine ethyl ester hydrochloride and 4.48 ml of N-ethylmorpholine were added and the mixture was allowed to come to room temperature, whereafter it was stirred for 4 hours. The solvent was removed by evaporation and the residue was partitioned between 200 ml of ethyl acetate and 100 ml of water. The organic phase was washed in sequence twice with 25 ml of 10% citric acid solution each time, twice with 25 ml of saturated sodium hydrogen carbonate solution each time, once with 25 ml of water and once with 25 ml of saturated sodium chloride solution, dried and evaporated. The resulting gum crystallized from ethyl acetate/n-hexane. There were obtained 13 g (77%) of Nα -tert.butoxycarbonyl-Nε -benzyloxycarbonyl-L-lysyl-L-alanine ethyl ester. Rf (chloroform/methanol 9:1) 0.73.

Workup

  1. additionwere added
  2. customto come to room temperature, whereafter it
  3. customThe solvent was removed by evaporation
  4. customthe residue was partitioned between 200 ml of ethyl acetate and 100 ml of water
  5. washThe organic phase was washed in sequence twice with 25 ml of 10% citric acid solution each time
  6. dry with materialtwice with 25 ml of saturated sodium hydrogen carbonate solution each time, once with 25 ml of water and once with 25 ml of saturated sodium chloride solution, dried
  7. customevaporated
  8. customThe resulting gum crystallized from ethyl acetate/n-hexane

Sources & evidence

ORD record
ord-a8f94009b5754dcd813ee3f3738a7555
Source dataset
uspto-grants-1991_02
Patent number
US04996358

Reaction notes

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