Reacción #8194

Ecuación de reacción

{1-methyl-2-[7-hydroxy-1H-indol-3-yl]ethyl}-carbamic acid tert-butyl ester

{1-methyl-2-[7-(benzyloxy)-1H-indol-3-yl]ethyl}-carbamic acid tert-butyl ester

bromoacetonitrile

potassium carbonate

→

racemic {1-methyl-2-[7-cyanomethoxy-1H-indol-3-yl]ethyl}-carbamic acid tert-butyl ester

Rendimiento 70.2%

Disolventes

methyl ethyl ketone

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe solids are removed by filtration
2. 2
   Lavadothe cake is washed with methyl ethyl ketone
3. 3
   Concentraciónthe combined filtrates are concentrated by rotary evaporation
4. 4
   OtroThe crude product is purified by flash chromatography (500 g silica gel, eluted with 8×500 mL dichloromethane, 4×500 mL 5% ethyl acetate/dichloromethane, 6×500 mL 10% ethyl acetate/dichloromethane)
5. 5
   workup.ADDITIONThe fractions containing product
6. 6
   Concentraciónare concentrated
7. 7
   workup.ADDITIONhexane is added to the solution
8. 8
   Otroto precipitate out the product

Procedimiento

The crude {1-methyl-2-[7-hydroxy-1H-indol-3-yl]ethyl}-carbamic acid tert-butyl ester from above (29.2 g, 102 mmol theory) is dissolved in methyl ethyl ketone (300 mL) and bromoacetonitrile (20.4 mL, 306 mmol) and potassium carbonate (33.8 g, 250 mmol) is added. The mixture is heated at 80° C. for 2 hours. The solids are removed by filtration, the cake is washed with methyl ethyl ketone, and the combined filtrates are concentrated by rotary evaporation. The crude product is purified by flash chromatography (500 g silica gel, eluted with 8×500 mL dichloromethane, 4×500 mL 5% ethyl acetate/dichloromethane, 6×500 mL 10% ethyl acetate/dichloromethane). The fractions containing product are concentrated and hexane is added to the solution to precipitate out the product affording 23.7 g (70.2% yield) of racemic {1-methyl-2-[7-cyanomethoxy-1H-indol-3-yl]ethyl}-carbamic acid tert-butyl ester.

Fuente