تفاعل #9667

معادلة التفاعل

HCl

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

isoamyl nitrite

→

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

المردود 48.0%

المذيبات

—

tri(ethylene glycol) dimethyl ether

acetonitrile

acetonitrile

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGThe reaction mixture was stirred at rt for 10 minutes
2. 2
   درجة الحرارةheated at 50° C. for 2.5 h
3. 3
   درجة الحرارةThe reaction mixture was cooled to rt
4. 4
   استخلاصThe solution was extracted with EtOAc
5. 5
   غسيلThe organic layer was washed with HCl (1.0 M), water and brine
6. 6
   ترشيحfiltered
7. 7
   تركيزconcentrated
8. 8
   أخرىThe residue was purified by flash chromatography (Biotage Flash 40M)

الإجراء التجريبي

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).

المصدر