Methanol → HCID 53689027, compound

HRID 442004Notes

Reaction equation

HRID 442004 reaction equation
C[O:2][C:3](=O)[C@H:4]([CH2:21][CH:22]([CH3:24])[CH3:23])[NH:5][C:6](=[O:20])[C@@H:7]([CH:17]=C=O)[NH:8]OCC1C=CC=CC=1.[H][H].[C:28]([O:32][C:33]([NH:35][C@H:36]([C:52]([OH:54])=O)[CH2:37][C:38]1[CH:43]=[CH:42][C:41]([O:44][CH2:45][C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)=[CH:40][CH:39]=1)=[O:34])([CH3:31])([CH3:30])[CH3:29].[CH3:55][OH:56]>[Pd]>[CH3:55][O:56][C:3](=[O:2])[C@H:4]([CH2:21][CH:22]([CH3:24])[CH3:23])[NH:5][C:6](=[O:20])[C@@H:7]([CH3:17])[NH:8][C:52](=[O:54])[C@H:36]([CH2:37][C:38]1[CH:39]=[CH:40][C:41]([O:44][CH2:45][C:46]2[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=2)=[CH:42][CH:43]=1)[NH:35][C:33]([O:32][C:28]([CH3:29])([CH3:30])[CH3:31])=[O:34]

Participants

6

Reactant 4

HCID 887MethanolHCID 98763O-benzyl-N-((tert-butoxy)carbonyl)-L-tyrosineHCID 86735014HCID 86735014, compoundHCID 178418361HCID 178418361, compound2×

Product 1

HCID 53689027HCID 53689027, compound

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Conditions

Temperature
-10 °C

Procedure

Nα -t-Butoxycarbonyl-O-benzyl-L-tyrosyl-D-alanyl-L-leucine methyl ester is prepared from 7 g. (20 mmol) of Nα -benzyloxy-carbonyl-D-alanyl-L-leucine methyl ester by reduction with hydrogen. The material is dissolved in 150 ml. of methanol and 500 mg. of 20% palladium-on-carbon added followed by the introduction of hydrogen. The stirred reaction mixture is shown by thin layer chromatography to be complete in 2 hours. The mixture is filtered to separate the catalyst and 7.42 g. (20 mmol) of Nα -t-butoxycarbonyl-O-benzyl-L-tyrosine added. The methanol is removed by evaporation under reduced pressure and the residue dissolved in 50 ml. of dimethylformamide. The cooled solution is treated with 2.7 g. of 1-hydroxybenztriazole and 4.3 g. of dicyclohexylcarbodiimide. The mixture is stirred at -10° C. for two hours and then at room temperature for two and one-half days. The mixture is filtered, the solid rinsed and the solvent evaporated at 40° C. under reduced pressure. The residue is dissolved in 300 ml. of ether and 50 ml. of ethyl acetate and washed three times with 5% sodium bicarbonate solution, saturated salt solution, dried over magnesium sulfate and evaporated. The residue crystallizes from ether-petroleum ether. The product is further purified by boiling with ether, cooling and filtering; 8.55 g. of white solid; m.p. 128°-129° C.

Workup

  1. dissolutionThe material is dissolved in 150 ml
  2. customThe stirred reaction mixture
  3. filtrationThe mixture is filtered
  4. customto separate the catalyst and 7.42 g
  5. customThe methanol is removed by evaporation under reduced pressure
  6. dissolutionthe residue dissolved in 50 ml
  7. additionThe cooled solution is treated with 2.7 g
  8. customat room temperature
  9. filtrationThe mixture is filtered
  10. washthe solid rinsed
  11. customthe solvent evaporated at 40° C. under reduced pressure
  12. dissolutionThe residue is dissolved in 300 ml
  13. washof ethyl acetate and washed three times with 5% sodium bicarbonate solution, saturated salt solution
  14. dry with materialdried over magnesium sulfate
  15. customevaporated
  16. customThe residue crystallizes from ether-petroleum ether
  17. customThe product is further purified
  18. temperaturecooling
  19. filtrationfiltering

Sources & evidence

ORD record
ord-b503f1fa07bc4c3a88a4833ffaa97131
Source dataset
uspto-grants-1977_08
Patent number
US04043994

Reaction notes

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