Diisopropylcarbodiimide → HCID 57582410, compound

In a 500 mL round-bottom flask, 4-chloro-2-methylbenzonitrile (10 g, 66 mmol) was dissolved in 200 mL of methanol. To the mixture was added hydroxylammonium chloride (4.56 g, 66 mmol) followed by DIEA (diisopropylethylamine) (23 mL, 132 mmol). The mixture was heated at reflux for overnight. The solvents were removed. The residue was dissolved in 200 mL of CHCl3. To the mixture was added 2-furoyl chloride (10.5 ml, 66 mmol) followed by DIEA (23 mL, 132 mmol). After reaction completion, the mixture was extracted with chloroform and water. The organic layer was separated, washed with brine, dried over Na2SO4, filtered and evaporated to dryness. The residue was dissolved in 200 mL of dioxanes. To the mixture was added 1 eq of DIC (N,N′-diisopropylcarbodiimide) followed by 1 eq of DIEA. The mixture was then heated at reflux overnight. After reaction completion, the mixture was cooled down. The solvents were removed in vacuo. The residue was then extracted with ethyl acetate and water. The organic layer was separated, washed with brine, dried over Na2SO4, filtered and evaporated to dryness. The crude was purified by flash chromatography on silica gel in a 0-20% ethyl acetate/hexanes gradient to afford 4.96 g of the desired compound 3-(4-Chloro-2-methyl-phenyl)-5-furan-2-yl-[1,2,4]oxadiazole as a white powder in an overall yield of 28.8%.

1. temperatureThe mixture was heated
2. temperatureat reflux for overnight
3. customThe solvents were removed
4. dissolutionThe residue was dissolved in 200 mL of CHCl3
5. customAfter reaction completion
6. extractionthe mixture was extracted with chloroform and water
7. customThe organic layer was separated
8. washwashed with brine
9. dry with materialdried over Na2SO4
10. filtrationfiltered
11. customevaporated to dryness
12. dissolutionThe residue was dissolved in 200 mL of dioxanes
13. temperatureThe mixture was then heated
14. temperatureat reflux overnight
15. customAfter reaction completion
16. temperaturethe mixture was cooled down
17. customThe solvents were removed in vacuo
18. extractionThe residue was then extracted with ethyl acetate and water
19. customThe organic layer was separated
20. washwashed with brine
21. dry with materialdried over Na2SO4
22. filtrationfiltered
23. customevaporated to dryness
24. customThe crude was purified by flash chromatography on silica gel in a 0-20% ethyl acetate/hexanes gradient

ORD record

ord-fa18bf31c78744ef8968e66550fd4615

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09125410B2