2-Indanone → HCID 18602841, compound

Glycyl-L-proline methylester hydrochloride (16.0 g, 72.1 m mole) was dissolved in methanol (150 ml), and Indan-2-on (4.75 g, 36.0 m mole) and triethylamine (1.8 g, 18.0 m mole) were added thereto. Sodium syanoborohydride (2.27 g, 36.0 m mole) was gradually added thereto while cooling with ice and stirring. The mixture was stirred for 1 hour while cooling with ice and next for 5 hours at room temperature. A little insoluble material was separated by filtration, and the filtrate was concentrated under reduced pressure. To the residue, water (100 ml) and ethyl ether (100 ml) were added, and the solution was adjusted to pH 1.5 with 6N hydrochloric acid while stirring to dissolve it. The ethyl ether layer was removed, and the remaining water layer was washed with ethyl ether (100 ml). The desired product was extracted from the water layer with chloroform (100 ml×3 times). The thus obtained chloroform as extracted was concentrated under reduced pressure until a tar-like residuse was obtained. To thus produced tar-like residue ethyl ether and 5% sodium bicarbonate (200 ml) were added and the mixture was stirred to dissolve the solid matter. The aqueous layer was removed and the ethyl ether layer was washed with an aqueous solution saturated with sodium chloride. To the ethyl ether layer water (150 ml) was added, and the solution was adjusted to pH 1.5 with 6N hydrochloric acid while stirring and ethyl ether was removed. The water layer was washed with ethyl ether (100 ml) and to the water layer chloroform (200 ml) was added. The solution was adjusted to pH 8.0 with sodium bicarbonate while stirring. The aqueous layer was removed, and chloroform layer was dried with anhydrous sodium sulfate, and the sodium sulfate was separated by filtration. Separately, anhydrous hydrogen chloride gas was brown into the chloroform, and thus obtained hydrogen chloride chloroform solution was added to the above mentioned chloroform layer. After checking to ascertain that the pH of the solution had been preserved, a distillation was carried out under reduced pressure, to yield N-(2-indanyl)glycyl-L-proline methylester hydrochloride (4.50 g, 13.3 m mole, yield: 37%).

1. temperaturewhile cooling with ice
2. stirringThe mixture was stirred for 1 hour
3. customA little insoluble material was separated by filtration
4. concentrationthe filtrate was concentrated under reduced pressure
5. additionTo the residue, water (100 ml) and ethyl ether (100 ml) were added
6. stirringwhile stirring
7. dissolutionto dissolve it
8. customThe ethyl ether layer was removed
9. washthe remaining water layer was washed with ethyl ether (100 ml)
10. extractionThe desired product was extracted from the water layer with chloroform (100 ml×3 times)
11. extractionThe thus obtained chloroform as extracted
12. concentrationwas concentrated under reduced pressure until a tar-like residuse
13. customwas obtained
14. stirringthe mixture was stirred
15. dissolutionto dissolve the solid matter
16. customThe aqueous layer was removed
17. washthe ethyl ether layer was washed with an aqueous solution saturated with sodium chloride
18. additionTo the ethyl ether layer water (150 ml) was added
19. stirringwhile stirring
20. customethyl ether was removed
21. washThe water layer was washed with ethyl ether (100 ml) and to the water layer chloroform (200 ml)
22. additionwas added
23. stirringwhile stirring
24. customThe aqueous layer was removed
25. dry with materialchloroform layer was dried with anhydrous sodium sulfate
26. customthe sodium sulfate was separated by filtration
27. additionwas added to the
28. distillationa distillation

ORD record

ord-0777def0cb264e3082a62fabd97b571a

Source dataset

uspto-grants-1986_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04590178