4-Methylmorpholine → Z-Lys(Tos)-Glu(OBzl)-OBzl

Temperatur

-15 °C

4.18 Grams of H-Glu(OBzl)-OBzl.Tos was dissolved in 30 ml of dimethylformamide (DMF), then 1.21 ml of triethylamine (TEA) was added and the mixture was stirred under cooling. On the other hand, 4.35 g of Z-Lys(Tos)-OH was dissolved in 30 ml of tetrahydrofuran (THF), and 0.98 ml of N-methylmorpholine was added thereto, then this mixture was cooled to -15° C. and under stirring condition 1.27 ml of isobutyl chloroformate was added dropwise. 30 Seconds after the addition, then the cooled DMF solution mentioned above was added thereto and this mixture was stirred at 0° C. for 5 minutes, then at 40° C. in a water bath for 1 minute, further at 15° C. for 30 minutes. THF and DMF were removed from the reaction mixture under a reduced pressure, the residue thus obtained was extracted with ethyl acetate. The extract was washed with 1N-citric acid, a saturated aqueous solution of sodium chloride, a saturated aqueous solution of sodium hydrogencarbonate then a saturated aqueous solution of sodium chloride in this order, then was dried with anhydrous sodium sulfate, and ethyl acetate was removed distillation. The oily residue obtained was solidified by adding ethyl ether and reprecipitated from ethyl acetate-ether to obtain 5.37 g of the desired product.

1. temperatureunder cooling
2. additionwas added dropwise
3. addition30 Seconds after the addition
4. additionabove was added
5. stirringthis mixture was stirred at 0° C. for 5 minutes
6. waitfurther at 15° C. for 30 minutes
7. customTHF and DMF were removed from the reaction mixture under a reduced pressure
8. customthe residue thus obtained
9. extractionwas extracted with ethyl acetate
10. washThe extract was washed with 1N-citric acid
11. dry with materiala saturated aqueous solution of sodium chloride, a saturated aqueous solution of sodium hydrogencarbonate then a saturated aqueous solution of sodium chloride in this order, then was dried with anhydrous sodium sulfate, and ethyl acetate
12. customwas removed
13. distillationdistillation
14. customThe oily residue obtained
15. customreprecipitated from ethyl acetate-ether

ORD-Eintrag

ord-7636de50eefe455dba6c7bd5500ecc03

Quelldatensatz

uspto-grants-1984_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US04474754