Sulfolane → methyl 6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxylate

HRID 42505

Reaktionsgleichung

Reaktionsgleichung von HRID 42505
[Br:1][C:2]1[CH:3]=[C:4]([C:16]([O:18][CH3:19])=[O:17])[C:5]2[C:6]([CH:14]=O)=[CH:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=2[CH:10]=1.C1(C)C=CC(S(=O)=O)=CC=1.S1(CCCC1)(=O)=O.C([BH3-])#N.[Na+]>CN(C=O)C.O>[Br:1][C:2]1[CH:3]=[C:4]([C:16]([O:18][CH3:19])=[O:17])[C:5]2[C:6]([CH3:14])=[CH:7][N:8]([CH:11]([CH3:12])[CH3:13])[C:9]=2[CH:10]=1

Komponenten

7

Edukt 4

HCID 31347SulfolaneHCID 5003444Sodium cyanoborohydrideHCID 86677357methyl 6-bromo-3-formyl-1-isopropyl-1H-indole-4-carboxylateHCID 178427284HCID 178427284, Verbindung

Produkt 1

HCID 67464634methyl 6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxylateAusbeute 89,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a stirred solution of methyl 6-bromo-3-formyl-1-isopropyl-1H-indole-4-carboxylate (60 g, 185 mmol) in DMF (220 mL) was added p-toluenesulfonic acid mono hydride (4.57 g, 24 mmol), p-toluenesulfonyl hydrazide (44.8 g, 240 mmol) followed by sulfolane (220 mL). The mixture was stirred at 100° C. for 1 h. The contents were cooled to room temperature and then sodium cyanoborohydride (46.5 g, 740 mmol) was added portion wise over a period of 25 min. Then the mixture was stirred at 100° C. for 2 h. Then the reaction mixture was stirred for 16 h at room temperature. The reaction mixture was diluted with water and extracted with 20% EtOAc: Pet ether, finally organic layer was washed with cold water, brine solution dried over anhydrous Na2SO4 and concentrated. Crude compound was purified by column chromatography using silica gel (100-200 mesh) and 20% DCM: Pet ether as an eluent to afford desired product methyl 6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxylate (24 g, 89.2% purity), (16 g, and 62.2% purity). 1H NMR (CDCl3, 400 MHz) δ 1.486 (d, J=6.4 Hz, 6H), 2.361 (s, 3H), 3.947 (s, 3H), 4.535-4.602 (m, 1H), 7.080 (s, 1H), 7.619 (s, 1H), 7.684 (s, 1H). LCMS (ES+) m/z=310.07 (M+H)

Aufarbeitung

  1. temperatureThe contents were cooled to room temperature
  2. stirringThen the mixture was stirred at 100° C. for 2 h
  3. stirringThen the reaction mixture was stirred for 16 h at room temperature
  4. extractionextracted with 20% EtOAc
  5. washPet ether, finally organic layer was washed with cold water, brine solution
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated
  8. customCrude compound was purified by column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-e9d49779bb894004b06fed95826ce42e
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08536179B2

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