Formaldehyde → 7'-fluorospiro[furo[2,3-f][1,3]benzodioxole-7,3'-indol]-2'(1'H)-one

A solution of 7-fluoro-3-(6-hydroxy-1,3-benzodioxol-5-yl)-1,3-dihydro-2H-indol-2-one (2.00 g, 7.00 mmol) and paraformaldehyde (2.10 g, 61.0 mmol) in THF (50 mL) was degassed by bubbling through argon for one hour, followed by the slow addition of lithium diisopropylamide (48.8 mL, freshly made 0.50 M solution, 25 mmol) at −78° C. The mixture was stirred at ambient temperature overnight and quenched with saturated ammonium chloride (50.0 mL). The mixture was extracted with ethyl acetate (3×100 mL). The combined organic layers was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. The residue was dissolved in anhydrous ethyl acetate (50 mL) followed by the addition of tributylphosphine (2.10 mL, 8.00 mmol) and di-tert-butyl azodicarboxylate (1.90 g, 8.00 mmol) at 0° C. The reaction mixture was stirred at ambient temperature for 16 h and quenched with saturated ammonium chloride (30.0 mL). The organic layer was separated, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. The residue was dissolved in methanol (70.0 mL) followed by the addition of saturated sodium bicarbonate solution (30.0 mL). The resulted mixture was refluxed at 100° C. for one hour. After cooling down to ambient temperature, the mixture was extracted with ethyl acetate (3×50.0 mL). The combined organic layers was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. The residue was subjected to column chromatography (ethyl acetate/hexane, 1/5) to give the title compound (0.27 g, 17%): 1H NMR (300 MHz, DMSO-d6) δ 11.06 (s, 1H), 7.17-7.08 (m, 1H), 7.00-6.88 (m, 2H), 6.64 (s, 1H), 6.33 (s, 1H), 5.92-5.85 (m, 2H), 4.74 (d, 1H), 4.62 (d, 1H).

1. customby bubbling through argon for one hour
2. additionfollowed by the slow addition of lithium diisopropylamide (48.8 mL, freshly made 0.50 M solution, 25 mmol) at −78° C
3. customquenched with saturated ammonium chloride (50.0 mL)
4. extractionThe mixture was extracted with ethyl acetate (3×100 mL)
5. dry with materialThe combined organic layers was dried over anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationThe filtrate was concentrated in vacuo to dryness
8. dissolutionThe residue was dissolved in anhydrous ethyl acetate (50 mL)
9. stirringThe reaction mixture was stirred at ambient temperature for 16 h
10. customquenched with saturated ammonium chloride (30.0 mL)
11. customThe organic layer was separated
12. dry with materialdried over anhydrous sodium sulfate
13. filtrationfiltered
14. concentrationThe filtrate was concentrated in vacuo to dryness
15. dissolutionThe residue was dissolved in methanol (70.0 mL)
16. additionfollowed by the addition of saturated sodium bicarbonate solution (30.0 mL)
17. temperatureThe resulted mixture was refluxed at 100° C. for one hour
18. temperatureAfter cooling down to ambient temperature
19. extractionthe mixture was extracted with ethyl acetate (3×50.0 mL)
20. dry with materialThe combined organic layers was dried over anhydrous sodium sulfate
21. filtrationfiltered
22. concentrationThe filtrate was concentrated in vacuo to dryness

ORD 기록

ord-175cb51039a84a61be4a4d7334ee05f7

출처 데이터셋

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08106087B2