反应详情

A partial solution/suspension of 3-formyl-5-{4-[1-(hydroxymethyl)cyclopropyl]phenyl}-1H-indole-6-carbonitrile (236 mg, 0.746 mmol) in tetrahydrofuran/t-butanol (6 mL/6 mL) was treated with 2-methyl-2-butene (4 mL, 40 mmol) followed by a solution of sodium chlorite (942 mg, 11 mmol) and sodium phosphate (monobasic and monohydrate, 1585 mg, 11.48 mmol) in water (4 mL) via glass pipet. The reaction was stoppered and allowed to stir overnight at room temperature. After 16 hours, the reaction mixture was poured into half-diluted saturated aqueous ammonium chloride solution (50 mL) and extracted with ethyl acetate (three times). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure to yield 346 mg of the crude desired product. The crude material was diluted with methanol (25 mL) and the mixture was heated to reflux. The resulting solution was allowed to cool to room temperature slowly. As the solution was cooling, the sides of the flask were scratched with a glass pipette and stirred at room temperature for 4 hours resulting in a precipitate. The precipitate showed birefringence under the microscope and the mixture was allowed to stir overnight at room temperature (18 hours). After 18 hours, the mixture was filtered and the filter cake was washed with methanol (2 mL) and dried under high vacuum for 40 minutes yielding 127 mg (51%) of desired product as a crystalline solid. The melting point range was determined by a starting temperature of 250° C. and a gradient of 2° C./minute which produced a melting point of 270.9-271.6° C. (determined by the Buchi Melting Point B-545). MS (ES+) 331.4 (M−H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.35 (br. s, 1H), 12.33 (br. s, 1H), 8.29 (d, J=2.3 Hz, 1H), 8.09 (s, 1H), 8.05 (s, 1H), 7.48 (d, J=8.4 Hz, 2H), 7.43 (d, J=8.4 Hz, 2H), 4.73 (t, J=5.7 Hz, 1H), 3.60 (d, J=5.7 Hz, 2H), 0.86-0.93 (m, 2H), 0.78-0.85 (m, 2H).

1. waitAfter 16 hours
2. extractionextracted with ethyl acetate (three times)
3. washThe combined organic layers were washed with brine
4. dry with materialdried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customto yield 346 mg of the crude desired product
8. temperaturethe mixture was heated to reflux
9. temperatureto cool to room temperature slowly
10. temperatureAs the solution was cooling
11. stirringstirred at room temperature for 4 hours
12. customresulting in a precipitate
13. stirringto stir overnight at room temperature (18 hours)
14. waitAfter 18 hours
15. filtrationthe mixture was filtered
16. washthe filter cake was washed with methanol (2 mL)
17. customdried under high vacuum for 40 minutes