L-Glutamine → HCID 13819651, compound

Temperature

5 °C

H-Gln-OH (2 eq.) and NaHCO3 (2 eq.) were dissolved under stirring in water at maximum 45° C. and then cooled to about 5° C. Z-Val-OSu (1 eq.) was dissolved in MeCN and added in the aqueous solution in such way that the temperature did not rise above 10° C. The mixture was stirred for at least 1 h at ±5° C. before being warmed to room temperature for at least two hours. The peptide solution was concentrated under vacuum, diluted with water and washed twice with AcOEt. The aqueous phase was then diluted with i-BuOH and the pH was adjusted to 2.5 with a solution of KHSO4. DCM was then added to extract the peptide into the organic phase which was washed with a 5% weight NaCl solution and finally with water. The organic phase was collected and concentrated under reduced pressure until water content in the evaporates was <1% weight. The concentrate was diluted with hot isopropyl acetate and left to cool to 25° C. under gentle stirring to crystallize the peptide. The solid was recovered by filtration, once washed with AcOiPr at 25° C. and dried under vacuum until AcOiPr content in the peptide was ≦5% weight. After drying under vacuum not less than 70% of Z-Val-Gln-OH was recovered.

1. additionadded in the aqueous solution in such way that the temperature
2. customdid not rise above 10° C
3. temperaturebefore being warmed to room temperature for at least two hours
4. concentrationThe peptide solution was concentrated under vacuum
5. additiondiluted with water
6. washwashed twice with AcOEt
7. additionThe aqueous phase was then diluted with i-BuOH
8. additionDCM was then added
9. extractionto extract the peptide into the organic phase which
10. washwas washed with a 5% weight NaCl solution and finally with water
11. customThe organic phase was collected
12. concentrationconcentrated under reduced pressure until water content in the evaporates
13. additionThe concentrate was diluted with hot isopropyl acetate
14. waitleft
15. temperatureto cool to 25° C.
16. stirringunder gentle stirring
17. customto crystallize the peptide
18. filtrationThe solid was recovered by filtration
19. washonce washed with AcOiPr at 25° C.
20. dry with materialdried under vacuum until AcOiPr content in the peptide
21. dry with materialAfter drying under vacuum not less than 70% of Z-Val-Gln-OH
22. customwas recovered

ORD record

ord-c543d728a7fd4d0ca6cecae312c5d147

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09051349B2