L-Phenylalanine → N,N-Dibenzyl-L-phenylalanine

HRID 989457Notes

Reaction equation

HRID 989457 reaction equation
[NH2:1][C@H:2]([C:10]([OH:12])=[O:11])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:19](Br)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(=O)([O-])O.[Na+]>O.CO>[CH2:19]([N:1]([CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[C@H:2]([C:10]([OH:12])=[O:11])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

7

Reactant 4

HCID 6140L-PhenylalanineHCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 516892Sodium Bicarbonate

Product 1

HCID 10980880N,N-Dibenzyl-L-phenylalanineYield 214.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

L-Phenylalanine (16.5 g) and potassium carbonate (27.6 g) were added to a mixed solvent of methanol (100 ml) and water (100 ml). Then, benzyl bromide (68.4 g) was added to the obtained mixture, and they were stirred under heating and reflux for 3 hours. The reaction mixture was cooled to room temperature, and poured on ice/water. After the extraction with diethyl ether (300 ml), the obtained solution in diethyl ether was dried over anhydrous sodium sulfate. Sodium sulfate was filtered out. 4 N solution (25 ml) of dioxane in hydrochloric acid was added to the obtained solution in diethyl ether. After stirring under cooling on ice followed by the crystallization, the crystals were separated and washed with diethyl ether. The obtained crystals were added to a mixture of water (100 ml) and toluene (100 ml) to obtain a slurry. After the neutralization with a saturated aqueous sodium hydrogencarbonate solution followed by the division into layers, the product was extracted again with toluene. The obtained toluene layers were combined together and dried over anhydrous magnesium sulfate. Magnesium sulfate was filtered out and the solvent was evaporated under reduced pressure to obtain the intended benzyl ester of N,N-dibenzyl-L-phenylalanine (37.06 g) in a yield of 85%.

Workup

  1. temperatureunder heating
  2. temperaturereflux for 3 hours
  3. additionpoured on ice/water
  4. extractionAfter the extraction with diethyl ether (300 ml)
  5. dry with materialthe obtained solution in diethyl ether was dried over anhydrous sodium sulfate
  6. filtrationSodium sulfate was filtered out
  7. addition4 N solution (25 ml) of dioxane in hydrochloric acid was added to the obtained solution in diethyl ether
  8. stirringAfter stirring
  9. temperatureunder cooling on ice
  10. customfollowed by the crystallization
  11. customthe crystals were separated
  12. washwashed with diethyl ether
  13. additionThe obtained crystals were added to a mixture of water (100 ml) and toluene (100 ml)
  14. customto obtain a slurry
  15. extractionthe product was extracted again with toluene
  16. dry with materialdried over anhydrous magnesium sulfate
  17. filtrationMagnesium sulfate was filtered out
  18. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-40bd5b1d4714421192d73bf5316c2939
Source dataset
uspto-grants-2003_10
Patent number
US06639094B2

Reaction notes

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