Hydrochloric Acid → 2-Chloro-4-methylbenzothiazole

To a solution containing copper chloride (II) (1.96 g, 14.61 mmol) and tri(ethylene glycol) dimethyl ether (6 mL) in acetonitrile (100 mL) was added isoamyl nitrite (2.14 g, 18.27 mmol), and the reaction mixture was stirred at rt for 30 minutes. To this suspension was added dropwise a solution of 2-amino-4-methylbenzothiazole (2.0 g, 12.18 mmol) in tri(ethylene glycol) dimethyl ether (10 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 (400 mL). The solution was extracted with EtOAc. The organic layer was washed with HCl (1.0 M), water, brine, filtered and concentrated in vacuo. The residue was purified by flash chromatography (Biotage Flash 40M) using 5% ethyl acetate in hexane to afford 2-chloro-4-methyl-1,3-benzothiazole (1.6 g, 71%). 1H NMR (400 MHz, CD2Cl2) δ 2.70 (s, 3H), 7.32 (m, 2H), 7.64 (m, 1H).

1. stirringThe reaction mixture was stirred at rt for 10 minutes
2. temperatureheated at 50° C. for 2.5 h
3. temperatureThe reaction mixture was cooled to rt
4. extractionThe solution was extracted with EtOAc
5. washThe organic layer was washed with HCl (1.0 M), water, brine
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was purified by flash chromatography (Biotage Flash 40M)

ORD record

ord-a6f0c139990247d8a0ef5d9148b8a780

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08013166B2