Reaktion #425468

Reaktionsgleichung

ammonium chloride

sodium chlorite

sodium phosphate

2-methyl-2-butene

3-formyl-5-{4-[1-(hydroxymethyl)cyclopropyl]phenyl}-1H-indole-6-carbonitrile

→

desired product

Ausbeute 51.2%

6-cyano-5-{4-[1-(hydroxymethyl)cyclopropyl]phenyl}-1H-indole-3-carboxylic acid

Ausbeute 51.2%

Lösungsmittel

methanol

water

tetrahydrofuran t-butanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.WAITAfter 16 hours
2. 2
   Extraktionextracted with ethyl acetate (three times)
3. 3
   WaschenThe combined organic layers were washed with brine
4. 4
   Trocknendried over sodium sulfate
5. 5
   Filtrationfiltered
6. 6
   Einengenconcentrated under reduced pressure
7. 7
   Sonstigeto yield 346 mg of the crude desired product
8. 8
   Temperaturthe mixture was heated to reflux
9. 9
   Temperaturto cool to room temperature slowly
10. 10
    TemperaturAs the solution was cooling
11. 11
    workup.STIRRINGstirred at room temperature for 4 hours
12. 12
    Sonstigeresulting in a precipitate
13. 13
    workup.STIRRINGto stir overnight at room temperature (18 hours)
14. 14
    workup.WAITAfter 18 hours
15. 15
    Filtrationthe mixture was filtered
16. 16
    Waschenthe filter cake was washed with methanol (2 mL)
17. 17
    Sonstigedried under high vacuum for 40 minutes

Vorschrift

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).

Quelle