Preparation and application of 2-bromobenzothiazole-6-carboxylic acid ethyl ester_Kain Industrial Additive

Background and overview^[1]

Ethyl 2-bromobenzothiazole-6-carboxylate can be used as a pharmaceutical synthesis intermediate. If 2-bromobenzothiazole-6-carboxylic acid ethyl ester is inhaled, move the patient to fresh air; if skin contact occurs, remove contaminated clothing and rinse the skin thoroughly with soap and water. If discomfort occurs, Seek medical attention; if eye contact occurs, separate eyelids, rinse with running water or saline, and seek medical attention immediately; if ingested, rinse mouth immediately, do not induce vomiting, and seek medical attention immediately.

Preparation^[1]

Ethyl 2-bromobenzothiazole-6-carboxylate was prepared as follows: a suspension of CuBr2 (1.20 g, 5.40 mmol) in anhydrous acetonitrile (15 mL) was purged with nitrogen. The mixture was cooled in an ice bath and treated with t-BuONO (696 mg, 6.75 mmol). After stirring for a further 10 minutes at about 0 to 5°C, the mixture was reacted with 2-amino-1,3-benzothiazole-6-carboxylate (1.0 g, 4.5 mmol). The cooling bath was removed and the reaction mixture was stirred at room temperature for 2 hours. The mixture was then diluted with water (30 mL) and extracted with diethyl ether (100 mL × 2). The combined organic phases were filtered to remove copper salts, then washed with water (20 mL) and brine (20 mL), dried over Na2SO4 and concentrated to give the title compound, 2-bromobenzothiazole-6-carboxylic acid ethyl ester.

1HNMR (CDCl3, 400MHz): δ8.54 (d, 1H), 8.16 (dd, 1H), 8.02 (d, 1H), 4.42 (q, 2H), 1.42 (t, 3H).

Apply^[1]

Ethyl 2-bromobenzothiazole-6-carboxylate can be used as a pharmaceutical synthesis intermediate. For example, to prepare 2-[(trimethylsilyl)ethynyl]-1,3-benzothiazole-6-carboxylic acid ethyl ester, the specific steps are: add to the stirred 2-bromo-1,3-benzothiazole -To a solution of ethynyl-6-carboxylate (880 mg, 3.07 mmol) and ethynyltrimethylsilane (453 mg, 4.61 mmol) in toluene (15 mL) and TEA (5 mL), CuI was added at room temperature under a nitrogen atmosphere, (117 mg, 0.61mmol), Pd(PPh3)2Cl2 (216mg, 0.31mmol) and PPh3 (81mg, 0.31mmol). The reaction mixture was stirred at 60°C for 4 hours. After cooling, the mixture was filtered and the solid was washed with EtOAc (200 mL). The combined organic phases were concentrated. The crude residue was purified by silica gel column chromatography (PE/EA=50:1) to obtain the title compound. 1HNMR (CDCl3, 400MHz): δ8.58 (d, 1H), 8.11 (dd, 1H), 8.01 (d, 1H), 4.36 (q, 2H), 1.42 (t, 3H), 0.32 (s, 9H) .

Main reference materials

[1] US20110166152 HETEROAROMATIC COMPOUNDS AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE