Reaction #9663

Reaction equation

HCl

isoamyl nitrite

4,6-difluoro-1,3-benzothiazol-2-amine

→

2-chloro-4,6-difluoro-1,3-benzothiazole

Yield 99.0%

Solvents

acetonitrile

—

tri(ethylene glycol) dimethyl ether

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 down

Procedure

To a solution containing copper chloride (II) (0.87 g, 6.45 mmol) and tri(ethylene glycol) dimethyl ether (3 mL) in acetonitrile (50 mL) was added isoamyl nitrite (0.94 g, 8.06 mmol), and the reaction mixture was stirred at rt for 30 minutes. To this suspension was added dropwise a solution of 4,6-difluoro-1,3-benzothiazol-2-amine (1.0 g, 5.37 mmol) in tri(ethylene glycol) dimethyl ether (5 mL). The reaction mixture was stirred at rt for 10 minutes, and then 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 (200 mL). The solution was extracted with EtOAc. The organic layer was washed with HCl (1.0 M), water and brine, filtered and concentrated down to afford 2-chloro-4,6-difluoro-1,3-benzothiazole (1.1 g, 99%). 1H NMR (400 MHz, DMSO-d6) 7.05 (m, 1H), 7.36 (m, 1H).

Source