Triethylamine → L-Alanyl-L-proline

온도

-15 °C

L-proline methylester hydrochloride (16.58 g, 100 mmole) was dissolved in chloroform (300 ml), and triethylamine (10.12 g, 100 mmole), 1-hydroxybenzotriazole (13.51 g, 100 mmole) and N-benzyloxycarbonyl-L-alanine (22.32 g, 100 mmole) were added thereto under cooling to -15° C. and stirring. To the solution, while keeping the temperature to less than 0° C., a chloroform solution of N,N'-dicyclohexylcarbodiimide (20.63 g, 100 mmole) was added dropwise. After that, the mixture was stirred for 2 hours at 0° C. and then overnight at room temperature. The thus precipitated N,N'-dicyclohexylurea was separated by filtration, and the solution was washed with 10% aqueous sodium bicarbonate, water, 1N hydrochloric acid and water in the order given, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and to the residue thus obtained 1N sodium hydroxide (150 ml) was added. The mixture was stirred for 3 hours at 30° C. The thus precipitated N,N'-dicyclohexylurea was separated by filtration, and the filtrate was adjusted to pH 2.5 with 6N hydrochloric acid and was extracted twice with chloroform (200 ml). The chloroform layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The thus obtained residue was dissolved in 50% methanol (300 ml), and-hydrogen gas was passed through the solution in the presence of 2% palladium-carbon as a catalyst for 2 hours at 40° C. The catalyst was separated by filtration and the solvent was distilled off under reduced pressure The residue thus obtained was recrystallized from water and ethanol to give L-alanyl-L-proline (13.41 g; 72.0%).

1. customto less than 0° C.
2. stirringAfter that, the mixture was stirred for 2 hours at 0° C.
3. customovernight
4. customat room temperature
5. customThe thus precipitated N,N'-dicyclohexylurea was separated by filtration
6. washthe solution was washed with 10% aqueous sodium bicarbonate, water, 1N hydrochloric acid and water in the order
7. dry with materialdried over anhydrous sodium sulfate
8. distillationThe solvent was distilled off under reduced pressure and to the residue thus obtained 1N sodium hydroxide (150 ml)
9. additionwas added
10. stirringThe mixture was stirred for 3 hours at 30° C
11. customThe thus precipitated N,N'-dicyclohexylurea was separated by filtration
12. extractionwas extracted twice with chloroform (200 ml)
13. dry with materialThe chloroform layer was dried over anhydrous sodium sulfate
14. distillationthe solvent was distilled off under reduced pressure
15. dissolutionThe thus obtained residue was dissolved in 50% methanol (300 ml)
16. customThe catalyst was separated by filtration
17. distillationthe solvent was distilled off under reduced pressure The residue
18. customthus obtained
19. customwas recrystallized from water and ethanol

ORD 기록

ord-6d82e5f927ff4a86b3ff9554d47921b7

출처 데이터셋

uspto-grants-1990_11

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US04971993