Ethanol → N-(2-indanyl)glycyl-L-proline benzylester

Glycyl-L-proline benzylester hydrochloride (20.0 g, 64.1 m mole) was dissolved in dried ethanol (150 ml) and indan-2-on (4.23 g, 32.1 m mole), and Molecular Sieves (3A) (5 g) were added thereto. Sodium cyanoborohydride (2.01 g, 32.1 m mole) was gradually added to the above solution while cooling with ice, and stirring. The mixture was stirred for 1 hour under cooling with ice and then stirred for 2 hours at room temperature. A little insoluble material was separated by filtration. The ethanol was removed by distillation under reduced pressure from the reaction solution. To the residue water (150 ml) and ethyl ether (200 ml) were added and the solution was adjusted to pH 1.5 with 6N hydrochloric acid while stirring to dissolve it. The ethylether layer was removed and the remaining water layer was washed with ethyl ether (200 ml). Next, to the water layer ethyl ether (400 ml) was added and the solution was adjusted to pH 8.0 with sodium bicarbonate aqueous solution. The desired product was extracted with ethyl ether and the ethyl ether layer was separated. Further, the desired product was extracted by the addition of ethyl ether (200 ml) to the water layer and the thus extracted ethyl ether solution was separated. Such extracted ethyl ether layers were combined together, and washed with the aqueous solution saturated with sodium chloride (100 ml). The ethyl ether layer was dried with anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crystal. The crystal was washed with n-hexane, obtained on the filter paper and dried to yield a white crystal of N-(2-indanyl)glycyl-L-proline benzylester (8.02 g, 21.2 m mole, yield: 33%). Melting point: 96°-98° C.

1. temperaturewhile cooling with ice
2. stirringThe mixture was stirred for 1 hour
3. temperatureunder cooling with ice
4. stirringstirred for 2 hours at room temperature
5. customA little insoluble material was separated by filtration
6. customThe ethanol was removed by distillation under reduced pressure from the reaction solution
7. additionTo the residue water (150 ml) and ethyl ether (200 ml) were added
8. stirringwhile stirring
9. dissolutionto dissolve it
10. customThe ethylether layer was removed
11. washthe remaining water layer was washed with ethyl ether (200 ml)
12. additionNext, to the water layer ethyl ether (400 ml) was added
13. extractionThe desired product was extracted with ethyl ether
14. customthe ethyl ether layer was separated
15. extractionFurther, the desired product was extracted by the addition of ethyl ether (200 ml) to the water layer
16. customthe thus extracted ethyl ether solution was separated
17. washwashed with the aqueous solution saturated with sodium chloride (100 ml)
18. dry with materialThe ethyl ether layer was dried with anhydrous sodium sulfate
19. concentrationconcentrated under reduced pressure
20. customto obtain a crystal
21. washThe crystal was washed with n-hexane
22. customobtained on the filter paper
23. customdried

ORD record

ord-cf98105de2404655afeefca6a7130e0e

Source dataset

uspto-grants-1985_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04536395