4-Methylmorpholine → 2(R)-[1(S)-(tert-butoxycarbonyl)-4-phenylbutyl]-4-methylvalerohydrazide

HRID 651788Notes

Reaction equation

HRID 651788 reaction equation
[C:1]([O:5][C:6]([C@H:8]([C@@H:18]([CH2:22][CH:23]([CH3:25])[CH3:24])[C:19](O)=[O:20])[CH2:9]/[CH:10]=[CH:11]/[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)(OCC1C=CC=CC=1)N.O[N:38]1C2C=CC=CC=2N=[N:39]1.CN1CCOCC1.C(N=C=NCCCN(C)C)C>CN(C)C=O>[C:1]([O:5][C:6]([C@H:8]([C@@H:18]([CH2:22][CH:23]([CH3:25])[CH3:24])[C:19]([NH:38][NH2:39])=[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

7

Reactant 5

HCID 79724-MethylmorpholineHCID 12136Benzyl carbamateHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 11418712(E)-2(R)-[1(S)-(tert-butoxycarbonyl)-4-phenyl-3-butenyl]-4-methylvaleric acid

Product 1

HCID 702001082(R)-[1(S)-(tert-butoxycarbonyl)-4-phenylbutyl]-4-methylvalerohydrazideYield 87.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 19 g of (E)-2(R)-[1(S)-(tert-butoxycarbonyl)-4-phenyl-3-butenyl]-4-methylvaleric acid in 220 ml of dimethylformamide was cooled to 0° C. and was treated in succession with 9.22 g of benzyl carbamate, 8.43 g of 1-hydroxybenzotriazole, 7.05 ml of N-methylmorpholine and 11.7 g of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. The mixture was allowed to warm to room temperature and was then stirred overnight. The solvent was evaporated and the residue was partitioned between ethyl acetate and 5% aqueous citric acid solution. The ethyl acetate layer was washed with 5% sodium hydrogen carbonate and saturated sodium chloride solution. After drying over anhydrous magnesium sulphate the ethyl acetate was evaporated and the residue dissolved 200 ml of methanol and 2.5 g of 10% palladium-on-charcoal added. The mixture was shaken in a hydrogen atmosphere for 4 hours and then the catalyst was removed by filtration. The methanol was evaporated and the residue stirred with hexane and filtered. There was obtained 17.41 g of 2(R)-[1(S)-(tert-butoxycarbonyl)-4-phenylbutyl]-4-methylvalerohydrazide in the form of a white solid.

Workup

  1. customThe solvent was evaporated
  2. customthe residue was partitioned between ethyl acetate and 5% aqueous citric acid solution
  3. washThe ethyl acetate layer was washed with 5% sodium hydrogen carbonate and saturated sodium chloride solution
  4. dry with materialAfter drying over anhydrous magnesium sulphate the ethyl acetate
  5. customwas evaporated
  6. dissolutionthe residue dissolved 200 ml of methanol and 2.5 g of 10% palladium-on-charcoal
  7. additionadded
  8. stirringThe mixture was shaken in a hydrogen atmosphere for 4 hours
  9. customthe catalyst was removed by filtration
  10. customThe methanol was evaporated
  11. stirringthe residue stirred with hexane
  12. filtrationfiltered

Sources & evidence

ORD record
ord-50414959bf534c8787c7fc5d4c893484
Source dataset
uspto-grants-2001_08
Patent number
US06281363B1

Reaction notes

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