Reacción #1350613

Ecuación de reacción

acetic anhydride

acetic anhydride

isoamylnitrite

18-crown-6

2-methyl-4-(hydroxymethyl)aniline

4-(hydroxymethyl)-2-methylaniline

compound 90

4-(hydroxymethyl)-2-methylaniline

potassium acetate

→

title compound

Rendimiento 92.2%

1-acetyl-5-(acetoxymethyl)indazole

Rendimiento 92.2%

Disolventes

methylene chloride

chloroform

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaThe mixture was then heated
2. 2
   Temperaturato reflux temperature for 2 hours under nitrogen
3. 3
   TemperaturaAfter cooling to room temperature
4. 4
   TemperaturaThe reaction mixture was heated at its
5. 5
   Temperaturareflux temperature for 28 hours
6. 6
   OtroAfter returning to room temperature
7. 7
   Lavadowashed with saturated aqueous NaHCO3 aqueous solution (300 mL), water (300 mL) and brine (50 mL)
8. 8
   SecadoAfter drying (Na2SO4)
9. 9
   Otrothe organic solvent was removed under vacuum
10. 10
    Otroto give a yellow oil which
11. 11
    Otrowas purified by flash chromatography on silica gel (85:15 hexane-ethyl acetate)

Procedimiento

To a suspension of 2-methyl-4-(hydroxymethyl)aniline (compound 90, 4.0 g, 29 mmol) and potassium acetate (Aldrich, 8.6 g, 88 mmol) in chloroform (Calbiochem, 60 mL), was added acetic anhydride (Aldrich, 8.3 mL, 88 mmol) at room temperature, and the temperature was allowed to increase to 45° C. The mixture was then heated to reflux temperature for 2 hours under nitrogen. After cooling to room temperature, isoamylnitrite (Aldrich, 7.8 mL, 88 mmol) and 18-crown-6 (Aldrich, 1.5 g, 0.6 mmol) were added. The reaction mixture was heated at its reflux temperature for 28 hours. After returning to room temperature, the mixture was further treated with acetic anhydride (10 mL) and the solution was stirred at room temperature for 12 hours. The reaction mixture was diluted with methylene chloride (600 mL) and washed with saturated aqueous NaHCO3 aqueous solution (300 mL), water (300 mL) and brine (50 mL). After drying (Na2SO4), the organic solvent was removed under vacuum to give a yellow oil which was purified by flash chromatography on silica gel (85:15 hexane-ethyl acetate) to yield the title compound (91, 6.21 g, 91%). TLC Rf 0.45 (70:30 hexane-ethyl acetate); MS (electrospray) 233 (M+1); 1H N MR (CDCl3) δ2.12 (s, 3H), 2.79 (app d, 3H, J=0.4 Hz), 5.23 (s, 2H), 7.56 (dd, 1H, J=8.8, 1.6 Hz), 7.74 (t, 1H, J=0.8 Hz), 8.12 (s, 1H), 8.43 (dd, 1H, J=8.8, 0.6 Hz).

Fuente