Ethylmorpholine → HCID 67863547, compound

HRID 476704Notes

Reaction equation

HRID 476704 reaction equation
C(OC(=O)[NH:10][C@H:11]([C:16](=[O:41])[NH:17][CH2:18][P:19]([O:39][CH3:40])([CH2:21][CH:22]([C:27](=[O:38])[NH:28][C@H:29]([C:34](=[O:37])[NH:35][CH3:36])[CH2:30][CH:31]([CH3:33])[CH3:32])[CH2:23][CH:24]([CH3:26])[CH3:25])=[O:20])[CH2:12][CH:13]([CH3:15])[CH3:14])C1C=CC=CC=1.[CH2:43]([O:50][C:51]([N:53]1[CH2:60][CH2:59][CH2:58][C@H:54]1[C:55]([OH:57])=O)=[O:52])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1.C(N1CCOCC1)C.OC1C2N=NNC=2C=CC=1.C1(N=C=NC2CCCCC2)CCCCC1>CO.Cl.CN(C)C=O.[Pd]>[CH3:40][O:39][P:19]([CH2:18][NH:17][C:16]([C@@H:11]([NH:10][C:55]([C@@H:54]1[CH2:58][CH2:59][CH2:60][N:53]1[C:51]([O:50][CH2:43][C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1)=[O:52])=[O:57])[CH2:12][CH:13]([CH3:15])[CH3:14])=[O:41])([CH2:21][CH:22]([C:27](=[O:38])[NH:28][C@H:29]([C:34](=[O:37])[NH:35][CH3:36])[CH2:30][CH:31]([CH3:33])[CH3:32])[CH2:23][CH:24]([CH3:26])[CH3:25])=[O:20]

Participants

10

Reactant 5

HCID 7525EthylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 101987Benzyloxycarbonyl-L-prolineHCID 131716205HCID 131716205, compoundHCID 178418300HCID 178418300, compound

Product 1

HCID 67863547HCID 67863547, compoundYield 112.7%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 313Hydrochloric AcidSolventHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

0.75 g of benzyl[(S)-1-[[[methoxy[(RS)-4-methyl-2-[[(S)-3-methyl-1-(methylcarbamoyl)butyl]carbamoyl]pentyl]phosphinyl]methyl]carbamoyl]-3-methylbutyl]carbamate was dissolved in 60 ml of methanol containing 1.4 ml of 1M hydrochloric acid. The solution was hydrogenated over 0.1 g of 10% palladium-on-charcoal for 4 hours. After filtration and evaporation, the residue was re-evaporated three times with 30 ml of toluene each time in order to remove water. The white residue obtained was dissolved in 10 ml of dimethylformamide and the solution was cooled to 0° C. 0.375 g of N-benzyloxycarbonyl-L-proline, 180 mg of N-ethylmorpholine and 0.4 g of hydroxybenzotriazole were added and, after all of the solids had dissolved, 0.345 g of N,N'-dicyclohexylcarbodiimide was added. After stirring at room temperature for 18 hours, the solvent was removed by evaporation. The residue was triturated with 30 ml of ethyl acetate and the mixture was filtered in order to remove dicyclohexylurea. The filtrate was washed twice with 30 ml of saturated sodium hydrogen carbonate solution each time, dried over anhydrous sodium sulfate and evaporated to give a colorless gum which was purified by flash chromatography on silica gel using 15% methanol in ethyl acetate for the elution. There was obtained 0.98 g of benzyl(S)-2-[[(S)-1-[[[methoxy[(RS)-4-methyl-2-[[(S)-3-methyl-1-(methylcarbamoyl)butyl]carbamoyl]pentyl]phosphinyl]methyl]carbamoyl]-3-methylbutyl]carbamoyl]-1-pyrrolidinecarboxylate in the form of a white foam.

Workup

  1. filtrationAfter filtration and evaporation
  2. customthe residue was re-evaporated three times with 30 ml of toluene each time in order
  3. customto remove water
  4. customThe white residue obtained
  5. dissolutionafter all of the solids had dissolved
  6. customthe solvent was removed by evaporation
  7. customThe residue was triturated with 30 ml of ethyl acetate
  8. filtrationthe mixture was filtered in order
  9. customto remove dicyclohexylurea
  10. washThe filtrate was washed twice with 30 ml of saturated sodium hydrogen carbonate solution each time
  11. dry with materialdried over anhydrous sodium sulfate
  12. customevaporated
  13. customto give a colorless gum which
  14. customwas purified by flash chromatography on silica gel using 15% methanol in ethyl acetate for the elution

Sources & evidence

ORD record
ord-3058c6453a324745b302975b0f1a4897
Source dataset
uspto-grants-1989_12
Patent number
US04885283

Reaction notes

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