Water → (2s)-Glycidyl indol-4-yl ether

A 3.2 g portion of 4-hydroxy-1H-indole was dissolved in 31 mL of dimethylformamide in a 50 mL flask equipped with a magnetic stirrer, nitrogen bubbler and thermometer. To it was added 1.27 g of sodium methoxide and the mixture was stirred until a blue-black solution resulted. The warm mixture was placed under vacuum for 5 minutes to remove most of the resulting methanol. To the mixture was added 6 g of oxiranylmethoxysulfonyl-3-nitrobenzene, resulting in an exotherm to about 37° C. The mixture was stirred at ambient temperature for 1 hour, and was then poured into a separatory funnel containing 55 mL of methyl t-butyl ether and 80 mL of water. The mixture was shaken well, and the layers were separated. The organic layer was removed and the aqueous layer was extracted with 2×55 mL of methyl t-butyl ether. The organic layers were combined and back-extracted with 50 mL of 5% aqueous lithium chloride. The layers were separated again, and the organic layer was dried with magnesium sulfate and filtered. The organic filtrate was concentrated under vacuum to about 15 mL of volume, and was seeded with pure desired product and stirred. The product was crystallized to a thick slurry to which 20 mL of heptane was slowly added. The mixture was stirred for one hour more and filtered, and the filter cake was rinsed with 3:1 heptane:methyl t-butyl ether, and then with heptane. The product was dried in a vacuum oven at 40° C. to obtain about 3.5 g of product.

1. customequipped with a magnetic stirrer
2. customresulted
3. customto remove most of the resulting methanol
4. additionTo the mixture was added 6 g of oxiranylmethoxysulfonyl-3-nitrobenzene
5. customresulting in an exotherm to about 37° C
6. stirringThe mixture was stirred at ambient temperature for 1 hour
7. additionwas then poured into a separatory funnel
8. stirringThe mixture was shaken well
9. customthe layers were separated
10. customThe organic layer was removed
11. extractionthe aqueous layer was extracted with 2×55 mL of methyl t-butyl ether
12. extractionback-extracted with 50 mL of 5% aqueous lithium chloride
13. customThe layers were separated again
14. dry with materialthe organic layer was dried with magnesium sulfate
15. filtrationfiltered
16. concentrationThe organic filtrate was concentrated under vacuum to about 15 mL of volume
17. stirringstirred
18. customThe product was crystallized to a thick slurry to which 20 mL of heptane
19. additionwas slowly added
20. stirringThe mixture was stirred for one hour more
21. filtrationfiltered
22. washthe filter cake was rinsed with 3:1 heptane
23. customThe product was dried in a vacuum oven at 40° C.

ORD record

ord-3f9118c93f564dd19c2cdbb54462387e

Source dataset

uspto-grants-1999_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05912256