Acetonitrile → 3-(4-Chlorobutyl)-5-cyanoindole

HRID 628800Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 628800
Cl[Si](C)(C)C.[Cl:6][CH2:7][CH2:8][CH2:9][C:10]([C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([C:21]#[N:22])[CH:19]=2)[NH:14][CH:13]=1)=O.C(#N)C.C([BH3-])#N.[Na+]>O>[Cl:6][CH2:7][CH2:8][CH2:9][CH2:10][C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([C:21]#[N:22])[CH:19]=2)[NH:14][CH:13]=1

Komponenten

6

Edukt 4

HCID 6342AcetonitrileHCID 6397ChlorotrimethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 102205283-(4-chlorobutanoyl)-1H-indole-5-carbonitrile

Produkt 1

HCID 98811233-(4-Chlorobutyl)-5-cyanoindole

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Chlorotrimethylsilane (137 g) was added to a mixture of 3-(4-chlorobutyryl)-1H-indole-5-carbonitrile (50 g) and acetonitrile (750 ml) at 25-30° C. The resulting mixture was cooled to 0° C., followed by portion wise addition of sodium cyanoborohydride (75 g) while maintaining the temperature at 0-5° C. during the time period of 30 minutes to 1 hour. The resulting mass was stirred for 1 hour at the same temperature. The temperature of the reaction mass was then raised to 25-30° C., followed by stifling for 6-16 hours at the same temperature. The reaction mass was slowly poured into water (5 Lt) at 25-30° C. and then stirred for 30 minutes to 1 hour at the same temperature. The separated solid was filtered and then dissolved in dichloromethane (900 ml) and the resulting organic layer was washed with 20% sodium chloride solution (400 ml×10). The resulting organic layer was subjected to carbon treatment, followed by distillation of the organic layer at 50-55° C. under vacuum to produce the titled compound as a residue. The resulting residue was dissolved in 5% aqueous methanol (4 to 5 times to the weight of the residue), followed carbon treatment at 50-55° C. The resulting filtrate was finally cooled to 25-30° C., the separated solid was filtered, washed with chilled 5% aqueous methanol (50 ml) and then dried the material at 60-65° C. to produce 31 g of 3-(4-chlorobutyl)-1H-indole-5-carbonitrile (First Crop). The resulting filtrate was cooled to 0-5° C. and then stirred for 30 minutes at the same temperature. The separated solid was filtered, washed with chilled 5% aqueous methanol and then dried the material at 60-65° C. to produce 10.5 g of the titled compound (Second Crop) (Purity by HPLC: 99.3; Total yield: 87.2%).

Aufarbeitung

  1. temperaturewhile maintaining the temperature at 0-5° C. during the time period of 30 minutes to 1 hour
  2. temperatureThe temperature of the reaction mass was then raised to 25-30° C.
  3. waitby stifling for 6-16 hours at the same temperature
  4. stirringstirred for 30 minutes to 1 hour at the same temperature
  5. filtrationThe separated solid was filtered
  6. dissolutiondissolved in dichloromethane (900 ml)
  7. washthe resulting organic layer was washed with 20% sodium chloride solution (400 ml×10)
  8. distillationfollowed by distillation of the organic layer at 50-55° C. under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-b7c9e480b0f246c4a0161049bd4ea094
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09315456B2

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