Hydrochloric Acid → Boc-Thr(Bzl)-Lys(COCH2CH2COOH)-OCH3

3.60 Grams of Z-Lys(COCH2CH2COOH)-OCH3 was dissolved in 30 ml of methanol, to this solution was added 100 mg of 5%-palladium-carbon and 9.13 ml of 1N-hydrochloric acid, and the mixture was subjected to a catalytic reduction in a hydrogen gas stream. After finishing the reaction, the catalyst was removed by filtration, and the filtrate was concentrated under reduced pressure, the residue thus obtained was dried over sodium hydroxide under reduced pressure. Then the residue thus obtained was dissolved in a mixture of 30 ml of THF and 5 ml of water, and under ice-cooling condition, the pH of this mixture was adjusted to pH 6-7 by adding triethylamine. To this mixture was added 4.08 g of Boc-Thr(Bzl)-OSu, then the pH of this mixture was adjusted to pH 7-8 by adding N-methylmorpholine, and stirred under ice-cooling condition for 1 hour, next at room temperature for 18 hours. The reaction mixture was concentrated under reduced pressure, and the residue thus obtained was extracted with 50 ml of ethyl acetate. The ethyl acetate layer was washed with 1N-hydrochloric acid, next with a saturated sodium chloride aqueous solution three times, then was dried over anhydrous sodium sulfate, and was concentrated under reduced pressure. The residue thus obtained was dissolved in chloroform and was added to a silica gel column, eluted with 200 ml of chloroform, next with 500 ml of 2%-methanol/chloroform to obtain the fraction containing the objective product, then concentrated under reduced pressure, and the residue thus obtained was solidified by adding diethyl ether. 960 Milligrams (yield: 19.1%) of the above-mentioned objective product was obtained.

1. customthe reaction
2. customthe catalyst was removed by filtration
3. concentrationthe filtrate was concentrated under reduced pressure
4. customthe residue thus obtained
5. dry with materialwas dried over sodium hydroxide under reduced pressure
6. customThen the residue thus obtained
7. temperatureunder ice-cooling condition
8. temperaturecooling condition for 1 hour
9. concentrationThe reaction mixture was concentrated under reduced pressure
10. customthe residue thus obtained
11. extractionwas extracted with 50 ml of ethyl acetate
12. washThe ethyl acetate layer was washed with 1N-hydrochloric acid, next with a saturated sodium chloride aqueous solution three times
13. dry with materialwas dried over anhydrous sodium sulfate
14. concentrationwas concentrated under reduced pressure
15. customThe residue thus obtained
16. additionwas added to a silica gel column
17. washeluted with 200 ml of chloroform, next with 500 ml of 2%-methanol/chloroform
18. customto obtain the fraction
19. additioncontaining the objective product
20. concentrationconcentrated under reduced pressure
21. customthe residue thus obtained

ORD record

ord-0330a9fd14674f41b921bf0ee77d0f83

Source dataset

uspto-grants-1993_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05204326