Ethylmorpholine → HCID 131716205, compound

HRID 476703Notes

Reaction equation

HRID 476703 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:17]([OH:19])=O)[CH2:13][CH:14]([CH3:16])[CH3:15])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N1CCOCC1)C.ClC(OCC(C)C)=O.[CH3:36][O:37][P:38]([CH2:58][NH2:59])([CH2:40][CH:41]([C:46](=[O:57])[NH:47][C@H:48]([C:53](=[O:56])[NH:54][CH3:55])[CH2:49][CH:50]([CH3:52])[CH3:51])[CH2:42][CH:43]([CH3:45])[CH3:44])=[O:39]>O1CCCC1.ClCCl>[CH2:1]([O:8][C:9](=[O:10])[NH:11][C@H:12]([C:17](=[O:19])[NH:59][CH2:58][P:38]([O:37][CH3:36])([CH2:40][CH:41]([C:46](=[O:57])[NH:47][C@H:48]([C:53](=[O:56])[NH:54][CH3:55])[CH2:49][CH:50]([CH3:52])[CH3:51])[CH2:42][CH:43]([CH3:44])[CH3:45])=[O:39])[CH2:13][CH:14]([CH3:15])[CH3:16])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 7525Ethylmorpholine2×HCID 62365Isobutyl chloroformateHCID 74840Leucine, N-carboxy-, N-benzyl ester, L-HCID 53878047HCID 53878047, compound

Product 1

HCID 131716205HCID 131716205, compoundYield 64%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 0.53 g of N-[(benzyloxy)carbonyl]-L-leucine in 10 ml of dry tetrahydrofuran was cooled to -30° C. and there was then added 0.23 g of N-ethylmorpholine followed by 0.27 g of isobutyl chloroformate. After stirring at -30° C. for 5 minutes a solution of 0.6 g of (aminomethyl)[(RS)-4-methyl-2-[[(S)-3-methyl-1-(methylcarbamoyl)butyl]carbamoyl]pentyl]phosphinic acid methyl ester, prepared as described in Example 2(A)(i), and 0.23 g of N-ethylmorpholine were added. The mixture was left to come to room temperature and was stirred at this temperature for 3.5 hours. The mixture was then diluted with 50 ml of dichloromethane, washed with 20 ml of 10% sulfuric acid, 20 ml of sodium chloride solution and 20 ml of saturated sodium hydrogen carbonate solution, dried over anhydrous sodium sulfate and evaporated to give a colorless gum. This gum was purified by flash chromatography on silica gel using 10% methanol in ethyl acetate for the elution to give 0.645 g of benzyl[(S)-1-[[[methoxy[(RS)-4-methyl-2-[[(S)-3-methyl-1-(methylcarbamoyl)butyl]carbamoyl]pentyl]phosphinyl]methyl]carbamoyl]-3-methylbutyl]carbamate in the form of a white foam.

Workup

  1. customprepared
  2. additionwere added
  3. waitThe mixture was left
  4. customto come to room temperature
  5. washwashed with 20 ml of 10% sulfuric acid, 20 ml of sodium chloride solution and 20 ml of saturated sodium hydrogen carbonate solution
  6. dry with materialdried over anhydrous sodium sulfate
  7. customevaporated
  8. customto give a colorless gum
  9. customThis gum was purified by flash chromatography on silica gel using 10% methanol in ethyl acetate for the elution

Sources & evidence

ORD record
ord-c90fd46a78c44f6bbb35f93332d68e3e
Source dataset
uspto-grants-1989_12
Patent number
US04885283

Reaction notes

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