Reacción #59164

Ecuación de reacción

HCl

5,7-difluoro-1,3-benzothiazol-2-amine

isoamyl nitrite

→

2-chloro-5,7-difluoro-1,3-benzothiazole

Rendimiento 48.0%

Disolventes

—

tri(ethylene glycol)dimethyl ether

acetonitrile

acetonitrile

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGThe reaction mixture was stirred at rt for 10 minutes
2. 2
   Temperaturaheated at 50° C. for 2.5 h
3. 3
   TemperaturaThe reaction mixture was cooled to rt
4. 4
   ExtracciónThe solution was extracted with EtOAc
5. 5
   LavadoThe organic layer was washed with HCl (1.0 M), water and brine
6. 6
   Filtraciónfiltered
7. 7
   Concentraciónconcentrated
8. 8
   OtroThe residue was purified by flash chromatography (Biotage Flash 40M)

Procedimiento

To a solution containing copper chloride (II) (0.89 g, 6.64 mmol) and tri(ethylene glycol)dimethyl ether (6 mL) in acetonitrile (60 mL) was added isoamyl nitrite (0.97 g, 8.30 mmol) and the reaction mixture was stirred at rt for 30 minutes. To this suspension was added dropwise a solution of 5,7-difluoro-1,3-benzothiazol-2-amine (1.03 g, 5.53 mmol) in tri(ethylene glycol)dimethyl ether (20 mL) and acetonitrile (30 mL). The reaction mixture was stirred at rt for 10 minutes and heated at 50° C. for 2.5 h. The reaction mixture was cooled to rt, and then poured cautiously into cold aqueous 6 M HCl (400 mL). The solution was extracted with EtOAc. The organic layer was washed with HCl (1.0 M), water and brine, filtered, and concentrated. The residue was purified by flash chromatography (Biotage Flash 40M) using 5% ethyl acetate in hexane to afford 2-chloro-5,7-difluoro-1,3-benzothiazole (0.55 g, 48%). 1H NMR (400 MHz, CD2Cl2) 7.02 (m, 1H), 7.52 (m, 1H).

Fuente