Reaktion #70783

Reaktionsgleichung

sulfolane

methyl 6-bromo-3-formyl-1-isopropyl-1H-indole-4-carboxylate

p-toluenesulfonic acid mono hydride

sodium cyanoborohydride

→

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

Ausbeute 89.2%

Lösungsmittel

water

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe contents were cooled to room temperature
2. 2
   workup.STIRRINGThen the mixture was stirred at 100° C. for 2 h
3. 3
   workup.STIRRINGThen the reaction mixture was stirred for 16 h at room temperature
4. 4
   Extraktionextracted with 20% EtOAc
5. 5
   WaschenPet ether, finally organic layer was washed with cold water, brine solution
6. 6
   Trocknendried over anhydrous Na2SO4
7. 7
   Einengenconcentrated
8. 8
   SonstigeCrude compound was purified by column chromatography

Vorschrift

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)

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