Реакция #10831

Уравнение реакции

3-(2,4-dimethoxy-phenyl)-4-isobutyl-4H-[1,2,4]triazole

dichloromethyl methyl ether

→

5-(4-isobutyl-4H-[1,2,4]triazol-3-yl)-2,4-dimethoxy-benzaldehyde

Выход 28.0%

Условия реакции

Обработка

1. 1
   workup.ADDITIONThe reaction mixture was poured into ice
2. 2
   ЭкстракцияThe aqueous solution was extracted with dichloromethane and isopropyl alcohol (33%, v/v, in dichloromethane)
3. 3
   ПромывкаThe combined dichloromethane and isopropyl alcohol were washed with brine
4. 4
   Сушкаdried over sodium sulfate
5. 5
   Концентрированиеconcentrated
6. 6
   workup.ADDITIONThe aqueous solution was treated with sodium hydroxide to pH 12
7. 7
   Экстракцияextracted again with isopropyl alcohol (33%, v/v, in dichloromethane)
8. 8
   Другоеto give additional product
9. 9
   ДругоеThe crude product was purified by flash chromatography
10. 10
    ПромывкаElution with methanol (10%, v/v, in dichloromethane)

Методика

Ex-109E: To a solution of 3-(2,4-dimethoxy-phenyl)-4-isobutyl-4H-[1,2,4]triazole (Ex-109D, 0.78 g, 2.98 mmol) was added dichloromethyl methyl ether (0.4 mL, 4.48 mmol) followed by addition of titanium tetrachloride (1.0M in dichloromethane, 9.0 mL, 9.0 mmol) over 10 min at 0° C. The reaction mixture was allowed to stir at 0° C. for 30 min and ambient temperature overnight. The reaction mixture was poured into ice. The aqueous solution was extracted with dichloromethane and isopropyl alcohol (33%, v/v, in dichloromethane). The combined dichloromethane and isopropyl alcohol were washed with brine, dried over sodium sulfate and concentrated. The aqueous solution was treated with sodium hydroxide to pH 12 and extracted again with isopropyl alcohol (33%, v/v, in dichloromethane) to give additional product. The crude product was purified by flash chromatography. Elution with methanol (10%, v/v, in dichloromethane) afford 5-(4-isobutyl-4H-[1,2,4]triazol-3-yl)-2,4-dimethoxy-benzaldehyde (0.24 g, 28%): 1H NMR (CDCl3) δ 10.30 (s, 1H), 8.17 (s, 1H), 7.90 (s, 1H), 6.51 (s, 1H), 4.00 (s, 3H), 3.87 (s, 3H), 3.58 (d, J=7.2 Hz, 2H), 1.91–1.80 (m, 1H), 0.77 (d, J=6.5 Hz, 6H).

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