2-BroMo-4,5,6,7-tetrahydro-benzothiazole-4-carboxylic acid ethyl ester synthesis

Yield:729590-69-6 33.1%

Reaction Conditions:

Stage #1: ethyl 2-amino-4,5,6,7-tetrahydrobenzo[d]thiazole-4-carboxylatewith sulfuric acid;copper(II) sulfate;sodium bromide in water at -10;
Stage #2: with sodium nitrite in water at 20;

Steps:

47 Preparation 47 2-Bromo-4,5, 6,7-tetrahydro-benzothiazole-4-carboxylic acid ethyl ester

To a solution of CuS04 11.6g, 72.7 mmol) and sulfuric acid (139 mL) in water (324 mL) is added 2-AMINO-4, 5,6, 7- tetrahydro-benzothiazole-4-carboxylic acid ethyl ester (11.3 g, 50 mmol) and a solution of sodium bromide (10.3 g, 100 mmol) in water (46 mL) at-10 oC. Then a solution of sodium nitrite (6 g, 87 mmol) in water (46 mL) is added beneath the reaction mixture surface via a TFE tubing connected at the tip of the additional funnel. After addition, the reaction mixture is warmed to room temperature. The reaction mixture is extracted with ether, combined organic layers are washed with water and brine, dried over sodium sulfate. Column chromatography on silica gel gave the title compound (4.8g, 33.1% yield).

References:

WO2004/63155,2004,A1 Location in patent:Page 91-92