Reacción #512923

Ecuación de reacción

methanol

4-[[(6-chloropyridin-3-yl)methyl]amino]furan-2(5H)-one

sodium hydride

3-bromo-1,1-dichloroprop-1-ene

→

4-[[(6-chloropyridin-3-yl)methyl](3,3-dichloroprop-2-en-1-yl)amino]furan-2(5H)-one

Rendimiento 50.7%

Disolventes

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturaunder reflux for 3 h
2. 2
   Temperaturathe mixture is heated
3. 3
   Temperaturaunder reflux for a further 5 h
4. 4
   TemperaturaAfter cooling of the reaction mixture to room temperature
5. 5
   Concentraciónthe mixture is concentrated under reduced pressure
6. 6
   Lavadothe mixture is washed successively twice with 1 N aqueous hydrochloric acid, twice with 1 N aqueous sodium hydroxide solution and once with saturated sodium chloride solution
7. 7
   SecadoThe organic phase is then dried over sodium sulphate
8. 8
   Concentraciónconcentrated under reduced pressure
9. 9
   OtroPurification of the residue by column chromatography on silica gel (silica gel 60—Merck, particle size: 0.04 to 0.063 mm)

Procedimiento

350 mg (1.56 mmol) of 4-[[(6-chloropyridin-3-yl)methyl]amino]furan-2(5H)-one (Ia-1; cf. EP 0539588 A1) and 124 mg (3.12 mmol) of a 60% dispersion of sodium hydride in mineral oil in 100 ml of tetrahydrofuran are heated under reflux for 3 h. After cooling to room temperature, 592 mg (3.12 mmol) of 3-bromo-1,1-dichloroprop-1-ene (cf. WO 8800183 A1) are added and the mixture is heated under reflux for a further 5 h. After cooling of the reaction mixture to room temperature and addition of methanol, the mixture is concentrated under reduced pressure. The residue is taken up in ethyl acetate and the mixture is washed successively twice with 1 N aqueous hydrochloric acid, twice with 1 N aqueous sodium hydroxide solution and once with saturated sodium chloride solution. The organic phase is then dried over sodium sulphate and concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel (silica gel 60—Merck, particle size: 0.04 to 0.063 mm) using the mobile phase mixture ethyl acetate:cyclohexane (2:1) gives 264 mg (50% of theory) of 4-[[(6-chloropyridin-3-yl)methyl](3,3-dichloroprop-2-en-1-yl)amino]furan-2(5H)-one.

Fuente