Reacción #76190

Ecuación de reacción

hydrochloric acid

water

2-(2-Methoxyphenoxy)ethylamine

4-(oxiran-2-ylmethoxy)-9H-carbazole

→

carvedilol

Disolventes

ethyl acetate

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe solid that formed
2. 2
   FiltraciónCarvedilol hydrochloride hydrate, is filtered
3. 3
   Lavadowashed with water (20 ml)
4. 4
   workup.ADDITIONwater (20 ml) containing 5% Sodium carbonate until the pH
5. 5
   OtroThe organic phase was separated
6. 6
   Secadodried over sodium sulfate
7. 7
   ConcentraciónThe dried solution was concentrated to a turbid solution
8. 8
   Temperaturacooled overnight to about 4° C

Procedimiento

2-(2-Methoxyphenoxy)ethylamine (III) (4.89 g) was heated to about 100° C., after which 4-(oxiran-2-ylmethoxy)-9H-carbazole (II) (3.31 g) was added portionwise. After approximately 20 minutes, the reaction mixture was cooled to about 70° C., after which water (25 ml) and ethyl acetate (15 ml) were added. The pH of the two-phase mixture was then adjusted to 5 with 2 N hydrochloric acid. The solid that formed, Carvedilol hydrochloride hydrate, is filtered, washed with water (20 ml) followed with ethylacetate (15 ml). The resulting material is reslurried in ethylacetate (50 ml) and water (20 ml) containing 5% Sodium carbonate until the pH reached 7.5. The organic phase was separated and dried over sodium sulfate. The dried solution was concentrated to a turbid solution and cooled overnight to about 4° C. Precipitated carvedilol was isolated by filteration and crystallized from isopropanol.

Fuente