Reaction #9667

Reaction equation

HCl

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

isoamyl nitrite

→

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

Yield 48.0%

Solvents

—

tri(ethylene glycol) dimethyl ether

acetonitrile

acetonitrile

Conditions

Workup

1. 1
   workup.STIRRINGThe reaction mixture was stirred at rt for 10 minutes
2. 2
   Temperatureheated at 50° C. for 2.5 h
3. 3
   TemperatureThe reaction mixture was cooled to rt
4. 4
   ExtractionThe solution was extracted with EtOAc
5. 5
   WashThe organic layer was washed with HCl (1.0 M), water and brine
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated
8. 8
   OtherThe residue was purified by flash chromatography (Biotage Flash 40M)

Procedure

To a solution containing copper chloride (H) (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).

Source