Continuously updated synthesis method about Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 651780-27-7, and friends who are interested can also refer to it.

In the chemical reaction process,reaction time,type of solvent,can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product.An updated downstream synthesis route of 651780-27-7,Ethyl 6-bromobenzo[d]isoxazole-3-carboxylate, as follows.651780-27-7

20a) Ethyl 6-(4-hydroxyphenyl)-l,2-benzisoxazole-3-carboxylateEthyl 6-bromo-l,2-benzisoxazole-3-carboxylate (0.34 g, 1.26 mmol), (4- hydroxyphenyl)boronic acid (0.21, 1.51 mmol), tetrakis(triphenylphosphine)palladium (0) (0.06 g, 0.05 mmol) and 2 M sodium carbonate (5 mL) in 1 ,2-dimethoxyethane (6 mL) were stirred at 80 0C for 1 hour. The reaction mixture was diluted with water, followed by ethyl acetate. The layers were separated and the ethyl acetate layer was washed with brine, dried over magnesium sulfate, filtered, and concentrated to afford the crude material. The crude material was purified using hexanes: ethyl acetate (0 to 40% ethyl acetate) to afford a mixture of desired product, plus the free acid of the desired product, 6-(4-hydroxyphenyl)-l,2- benzisoxazole-3-carboxylic acid. All the fractions were combined and concentrated. The mixture was then dissolved in ethanol. Thionyl chloride was added, and the reaction mixture was reflux for 8 days. The reaction mixture was cooled to room temperature and concentrated. The concentrated material was diluted with 5% sodium bicarbonate, and extracted with ethyl acetate. The ethyl acetate layer was washed with water followed by brine, dried over magnesium sulfate, filtered, and concentrated. The crude material was purified using hexanes: ethyl acetate (0 to 100% ethyl acetate) to afford 0.044 g (13%) of ethyl 6-(4-hydroxyphenyl)- 1 ,2-benzisoxazole-3- carboxylate. 1H NMR (400 MHz, d6-DMSO): delta 9.76 (s, IH), 8.05 (m, 2H), 7.79 (dd, J = 8, 1 Hz, IH), 7.65 (d, J = 9 Hz, 2H), 6.88 (d, J = 9 Hz, 2H), 4.47 (q, J = 7 Hz, 2H), 1.39 (t, J = 7 Hz, 3H).

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 651780-27-7, and friends who are interested can also refer to it.

Reference£º
Patent; SMITHKLINE BEECHAM CORPORATION; WO2008/157270; (2008); A1;,
Benzisoxazole – Wikipedia
Benzisoxazole – an overview | ScienceDirect Topics