Dabco → HCID 13001869, compound

HRID 2286326Notes

Reaction equation

HRID 2286326 reaction equation
[C:1]([O:5][C:6]([N:8]([CH3:28])[C@H:9]([C:25]([OH:27])=O)[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17]CC2C=CC=CC=2)=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].S(C1C=CC(C)=CC=1)([O-])(=O)=O.[NH2:40][C@@H:41]([C:43]([O:45]CC1C=CC=CC=1)=[O:44])[CH3:42].C1N2CCN(CC2)C1.C1CCC(N=C=NC2CCCCC2)CC1>CCOCC.CN(C=O)C>[C:1]([O:5][C:6]([N:8]([CH3:28])[C@H:9]([C:25]([NH:40][C@@H:41]([C:43]([OH:45])=[O:44])[CH3:42])=[O:27])[CH2:10][C:11]1[CH:12]=[CH:13][C:14]([OH:17])=[CH:15][CH:16]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 5

HCID 9237DabcoHCID 10868DicyclohexylcarbodiimideHCID 85570p-ToluenesulfonateHCID 726857D-Alanine, phenylmethyl esterHCID 7010604N-[(1,1-Dimethylethoxy)carbonyl]-N-methyl-O-(phenylmethyl)-L-tyrosine

Product 1

HCID 13001869HCID 13001869, compoundYield 99%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To 30 ml. of DMF were added 2.73 grams (7.1 mmoles) of Nα -t-butyloxycarbonyl-Nα -methyl-O-benzyl-L-tyrosine (prepared by acidification of 3.6 grams of the product from Part A and extraction into ether). The solution was cooled to 0° C., and 2.26 grams (7.1 mmoles) of the tosylate salt of D-alanine, benzyl ester, were added followed by 0.794 grams (7.1 mmoles) of triethylenediamine. The mixture was stirred at 0° C. for five minutes, and 0.96 grams of HBT and 1.46 grams (7.1 mmoles) of DCC were added. The mixture was stirred at 0° C. for two hours and then at room temperature for 24 hours. The mixture then was cooled to 0° C. and filtered. The filtrate was concentrated in vacuo to an oil, and then the oil was dissolved in ethyl acetate and extracted successively with 1 N aqueous sodium bicarbonate, water, 1.5 N citric acid, and water. The organic phase was dried over magnesium sulfate and concentrated in vacuo to an oil. The oil was dissolved in 60 ml. of ethanol, and 1.5 grams of 5% palladium on carbon were added to the mixture as a water slurry. Nitrogen was bubbled into the reaction mixture through a gas dispersion tube for five minutes followed by hydrogen gas for 24 hours. The mixture was flushed with nitrogen, and the catalyst was removed by filtration. The reaction mixture was concentrated in vacuo to an amorphous solid to give 2.5 grams (99 percent) of the title compound.

Workup

  1. stirringThe mixture was stirred at 0° C. for two hours
  2. waitat room temperature for 24 hours
  3. temperatureThe mixture then was cooled to 0° C.
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo to an oil
  6. dissolutionthe oil was dissolved in ethyl acetate
  7. extractionextracted successively with 1 N aqueous sodium bicarbonate, water, 1.5 N citric acid, and water
  8. dry with materialThe organic phase was dried over magnesium sulfate
  9. concentrationconcentrated in vacuo to an oil
  10. dissolutionThe oil was dissolved in 60 ml
  11. additionof ethanol, and 1.5 grams of 5% palladium on carbon were added to the mixture as a water slurry
  12. customNitrogen was bubbled into the reaction mixture through a gas dispersion tube for five minutes
  13. waitfollowed by hydrogen gas for 24 hours
  14. customThe mixture was flushed with nitrogen
  15. customthe catalyst was removed by filtration
  16. concentrationThe reaction mixture was concentrated in vacuo to an amorphous solid

Sources & evidence

ORD record
ord-f3af852b73624bc2b0021ab4a2029bd7
Source dataset
uspto-grants-1981_05
Patent number
US04265808

Reaction notes

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