Reacción #571692

Ecuación de reacción

3-chloro-6-methylpyridazine

ethyl 4-[2-(4-piperidinyl)ethoxy]benzoate butanedioate

sodium carbonate

N,N-dimethylformamide

→

ethyl 4-[2-[1-(6-methyl-3-pyridazinyl)-4-piperidinyl]ethoxy ]benzoate

Rendimiento 56.8%

Disolventes

dichloromethane

water

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaAfter cooling
2. 2
   Otrothe layers were separated
3. 3
   OtroThe organic layer was dried
4. 4
   Filtraciónfiltered
5. 5
   Otroevaporated
6. 6
   OtroThe residue was purified by column chromatography over silica gel using
7. 7
   workup.ADDITIONa mixture of trichloromethane and ethanol (99:1 by volume) as eluent
8. 8
   OtroThe pure fractions were collected
9. 9
   Otrothe eluent was evaporated
10. 10
    OtroThe residue was crystallized from a mixture of 2,2'-oxybixpropane and 2-propanone (75:25 by volume)
11. 11
    FiltraciónThe precipitated product as filtered off
12. 12
    Otrodried

Procedimiento

A mixture of 10.4 parts of 3-chloro-6-methylpyridazine, 22.4 parts of ethyl 4-[2-(4-piperidinyl)ethoxy]benzoate butanedioate (1:1), 8.6 parts of sodium carbonate and 0.9 parts of N,N-dimethylformamide was stirred for 3 hours in an oil bath at ±150° C. After cooling, water and dichloromethane were added and the layers were separated. The organic layer was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and ethanol (99:1 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from a mixture of 2,2'-oxybixpropane and 2-propanone (75:25 by volume). The precipitated product as filtered off and dried, yielding 17 parts (56.8%) of ethyl 4-[2-[1-(6-methyl-3-pyridazinyl)-4-piperidinyl]ethoxy ]benzoate; mp. 130.1° C. (comp. 1).

Fuente