Реакция #70787

Уравнение реакции

sulfolane

methyl 6-bromo-1-sec-butyl-3-formyl-1H-indole-4-carboxylate

p-toluenesulfonic acid mono hydrate

sodium cyanoborohydride

→

methyl 6-bromo-1-sec-butyl-3-methyl-1H-indole-4-carboxylate

Выход 54.6%

Растворители

water

DMF

Условия реакции

Обработка

1. 1
   ТемператураThe reaction mixture was cooled to room temperature
2. 2
   workup.STIRRINGstirred at 100° C. for 2 h
3. 3
   ТемператураThe reaction mixture was cooled to room temperature
4. 4
   workup.STIRRINGstirred at the same temperature for 16 h
5. 5
   Экстракцияextracted with 30% EtOAc
6. 6
   ПромывкаThe organic layer was washed with cold water (100 mL), brine (100 mL)
7. 7
   Сушкаdried over anhydrous Na2SO4
8. 8
   Концентрированиеconcentrated under reduced pressure
9. 9
   Другоеto afford crude, which
10. 10
    Другоеwas purified by column chromatography over silica gel (100-200 mesh)

Методика

To a stirred solution of methyl 6-bromo-1-sec-butyl-3-formyl-1H-indole-4-carboxylate (15 g, 44.6 mmol) in DMF (115 mL) was added p-toluenesulfonic acid mono hydrate (1.1 g, 5.8 mmol), p-toluenesulfonyl hydrazide (10.8 g, 58 mmol) followed by sulfolane (115 mL) at RT and the reaction mixture was stirred at 100° C. for 1 h. The reaction mixture was cooled to room temperature, treated with sodium cyanoborohydride (11.9 g, 178.5 mmol) portion wise over a period of 5 min and stirred at 100° C. for 2 h. The reaction mixture was cooled to room temperature and stirred at the same temperature for 16 h. The reaction mixture was diluted with water and extracted with 30% EtOAc: Pet ether. The organic layer was washed with cold water (100 mL), brine (100 mL) and dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford crude, which was purified by column chromatography over silica gel (100-200 mesh) using 5% EtOAc: Pet ether as eluent to afford title compound methyl 6-bromo-1-sec-butyl-3-methyl-1H-indole-4-carboxylate (7.88 g, 54.6%) as pale yellow gum. 1H NMR (CDCl3, 400 MHz): δ 0.804-0.841 (t, J=7.4 Hz, 3H), 1.454-1.470 (d, J=6.4 Hz, 3H), 1.865-1.884 (m, 2H), 2.363 (s, 3H), 3.950 (s, 3H), 4.265-4.316 (m, 1H), 7.038 (s, 1H), 7.609 (d, J=1.2 Hz, 1H), 7.671 (d, J=2 Hz, 1H). MS (ES+): 324.19 [M+H] ion present.

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