Sodium hydride → methyl 6-bromo-1-cyclobutyl-1H-indole-4-carboxylate

HRID 62412Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 62412
[Br:1][C:2]1[CH:3]=[C:4]([C:11]([O:13][CH3:14])=[O:12])[C:5]2[CH:6]=[CH:7][NH:8][C:9]=2[CH:10]=1.[Cl-].C(C[P+](C)(C)C)#N.[CH:23]1(O)[CH2:26][CH2:25][CH2:24]1.[H-].[Na+]>C1COCC1.CCOC(C)=O.CCCCCC>[Br:1][C:2]1[CH:3]=[C:4]([C:11]([O:13][CH3:14])=[O:12])[C:5]2[CH:6]=[CH:7][N:8]([CH:23]3[CH2:26][CH2:25][CH2:24]3)[C:9]=2[CH:10]=1

Komponenten

8

Edukt 4

HCID 24758Sodium hydrideHCID 76218CyclobutanolHCID 13770009methyl 6-bromo-1H-indole-4-carboxylateHCID 57431663(Cyanomethyl)trimethylphosphonium chloride

Produkt 1

HCID 67469195methyl 6-bromo-1-cyclobutyl-1H-indole-4-carboxylateAusbeute 25 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 8028TetrahydrofuranLösungsmittelHCID 8058HexaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

In an oven dried 100 ml RBF, equipped with a stir bar, septum, nitrogen inlet was added methyl 6-bromo-1H-indole-4-carboxylate (1.0 g, 3.94 mmol) and (cyanomethyl)(trimethyl)phosphonium chloride (1.491 g, 9.84 mmol). Added in THF (40 mL) and stirred suspension for 5 min. The reaction was cooled with an ice bath for 10 min, then was added cyclobutanol (0.616 mL, 7.87 mmol), followed by sodium hydride (0.346 g, 8.66 mmol) portionwise. The ice bath was removed and the reaction stirred at ambient temperature for 45 min, then heated at 50° C. for 18 h. LCMS showed mostly SM. Heated at 75° C. for 24 h. The reaction was allowed to cool to RT, then poured into water (200 ml) and extracted with EtOAc (2×). The combined organics were dried over magnesium sulfate, filtered, and concentrated. Purification of the residue by column chromatography (40 g Isco silica column; gradient B: 2-25%; A: hexane, B: EtOAc) gave methyl 6-bromo-1-cyclobutyl-1H-indole-4-carboxylate (0.3 g, 25% yield, ˜45% pure by HPLC). MS(ES) [M+H]+ 308.2.

Aufarbeitung

  1. customIn an oven dried 100 ml RBF
  2. customequipped with a stir bar
  3. temperatureThe reaction was cooled with an ice bath for 10 min
  4. customThe ice bath was removed
  5. stirringthe reaction stirred at ambient temperature for 45 min
  6. temperatureHeated at 75° C. for 24 h
  7. temperatureto cool to RT
  8. additionpoured into water (200 ml)
  9. extractionextracted with EtOAc (2×)
  10. dry with materialThe combined organics were dried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customPurification of the residue by column chromatography (40 g Isco silica column

Quellen und Nachweise

ORD-Eintrag
ord-10b8c53351c2410ba5b6e8f453bcf237
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09446041B2

Notizen zur Reaktion

Wird geladen…