Hydrochloric Acid → Z-Ala-gln-OH

HRID 1086940Notes

Reaction equation

HRID 1086940 reaction equation
[NH:1]([C:7]([O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:8])[C@H:2]([C:4]([OH:6])=O)[CH3:3].ON1C(=O)CCC1=O.C1(N=C=NC2CCCCC2)CCCCC1.[NH2:40][C@H:41]([C:47]([OH:49])=[O:48])[CH2:42][CH2:43][C:44](=[O:46])[NH2:45].Cl>O1CCOCC1.C(=O)([O-])O.[Na+]>[C:7]([NH:1][C@H:2]([C:4]([NH:40][C@H:41]([C:47]([OH:49])=[O:48])[CH2:42][CH2:43][C:44](=[O:46])[NH2:45])=[O:6])[CH3:3])([O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:8]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 5961L-GlutamineHCID 10868DicyclohexylcarbodiimideHCID 80170N-HydroxysuccinimideHCID 736104N-carbobenzyloxyalanine

Product 1

HCID 14534789Z-Ala-gln-OHYield 44.6%

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolvent3×HCID 516892Sodium BicarbonateSolvent

Procedure

Into a 300 mol round bottom flask were charged 10 g (44.8 mmol) of Z-L-Ala and 5.2 g (45.2 mmol) of N-hydroxysuccinimide, and the contents were dissolved in 100 ml of dioxane. Then, a solution of 9.2 g (44.7 mmol) of dicyclohexylcarbodiimide in 40 ml of dioxane was added dropwise, while the temperature of the reaction mixture wa maintained at 25° to 20° C. After the reaction had been allowed to proceed for 5 hours, precipitated dicyclohexylurea was filtered off. On the other hand, 7.2 g (50 mmol) of L-Gln was dissolved in 70 ml of aqueous 10% sodium hydrogencarbonate solution, and the resulting solution was cooled to 15° to 10° C. The dioxane solution prepared above was then added dropwise to the cooled solution, and the reaction was allowed to proceed for 5 hours. After the completion of the reaction, the pH of the reaction mixture was adjusted to 6.8 with lN HCl, and the dioxane was distilled off. After insoluble substances were filtered off, its pH was adjusted to 3 to 3.5 with 1N HCl. Crystals precipitated within 1 to 2 minutes, and the crystals were collected by filtration, washed with water and dried under reduced pressure to give 7 g (20 mmol) of Z-L-Ala-L-Gln. The pH of the above mother liquor was adjusted to 2.0 with lN HCl, so as to precipitate an additional 5 g of Z-L-Ala-L-Gln.

Workup

  1. temperaturewa maintained at 25° to 20° C
  2. customprecipitated dicyclohexylurea
  3. filtrationwas filtered off
  4. temperaturethe resulting solution was cooled to 15° to 10° C
  5. additionwas then added dropwise to the cooled solution
  6. waitto proceed for 5 hours
  7. customAfter the completion of the reaction
  8. distillationthe dioxane was distilled off
  9. filtrationAfter insoluble substances were filtered off
  10. customCrystals precipitated within 1 to 2 minutes
  11. filtrationthe crystals were collected by filtration
  12. washwashed with water
  13. customdried under reduced pressure

Sources & evidence

ORD record
ord-9de5b8f1c8864348a41c278897f100d6
Source dataset
uspto-grants-1991_07
Patent number
US05032675

Reaction notes

Loading…