Reaktion #340425

Reaktionsgleichung

sodium bicarbonate

hydrazine dihydrochloride

triethylamine

(2,3-bis{[2-(methyloxy)ethyl]oxy}phenyl)acetonitrile

sodium hydride

ethyl acetate

→

4-(2,3-bis{[2-(methyloxy)ethyl]oxy}phenyl)-3-methyl-1H-pyrazol-5-amine

Ausbeute 120.0%

Lösungsmittel

ethanol

water

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturAfter cooling to 0° C.
2. 2
   Waschenthe aqueous layer was washed with dichloro-methane (3×25 mL)
3. 3
   Extraktionextracted with ethyl acetate (3×50 mL)
4. 4
   WaschenThe ethyl acetate layer was washed with brine (50 mL)
5. 5
   Trocknendried with sodium sulfate
6. 6
   Einengenconcentrated
7. 7
   Sonstigeto give a yellow oil
8. 8
   TemperaturThe reaction mixture was refluxed for 90 min
9. 9
   Temperaturcooled to rt
10. 10
    ExtraktionThe aqueous layer was extracted with dichloromethane (3×50 mL)
11. 11
    Trocknenthe organic layer was dried with sodium sulfate
12. 12
    Einengenconcentrated

Vorschrift

To a solution of (2,3-bis{[2-(methyloxy)ethyl]oxy}phenyl)acetonitrile (0.93 g, 3.52 mmol) in THF (20 mL) was added sodium hydride (0.42 g, 10.56 mmol) and ethyl acetate (1.55 g, 17.60 mmol), and the mixture was stirred at 60° C. for 90 min. After cooling to 0° C., water was added (50 mL), the aqueous layer was washed with dichloro-methane (3×25 mL), acidified with 1N HCl to pH 3, and extracted with ethyl acetate (3×50 mL). The ethyl acetate layer was washed with brine (50 mL), dried with sodium sulfate, and concentrated to give a yellow oil. This oil was dissolved in dry ethanol (5 mL), and hydrazine dihydrochloride (0.44 g, 4.20 mmol) and triethylamine (0.22 g, 2.10 mmol) were added. The reaction mixture was refluxed for 90 min, cooled to rt, and added into sat. sodium bicarbonate (100 mL). The aqueous layer was extracted with dichloromethane (3×50 mL), the organic layer was dried with sodium sulfate, and concentrated. Column chromatography on silica (95:5 dichloromethane/methanol) afforded 4-(2,3-bis{[2-(methyloxy)ethyl]oxy}phenyl)-3-methyl-1H-pyrazol-5-amine (0.81 g, 71% yield) as a pale yellow oil. 1H NMR (400 MHz, d4-methanol) δ7.08 (t, 1H), 6.97 (dd, 1H), 6.85 (dd, 1H), 4.18 (m, 2H), 3.90 (m, 2H), 3.78 (m, 2H), 3.47 (m, 2H), 3.43 (s, 3H), 3.23 (s, 3H), 2.19 (s, 3H).

Quelle