65685-50-9

The general procedure for the synthesis of 5-bromobenzo[d]isoxazol-3(2H)-one from the compound (CAS:5798-94-7) was as follows: thionyl chloride (10 ml) was added slowly and dropwise to a solution of δ-bromosalicylcarbamic acid F2 (21.6 g) in tetrahydrofuran (60 ml) under stirring conditions at 10-200 °C. Stirring of the reaction mixture was continued for 2 hours by maintaining the same temperature. Subsequently, the reaction mixture was evaporated under reduced pressure to remove the solvent, the residue was dissolved in dioxane (60 ml) and the solution was cooled to 0-50 °C. To this cooled reaction mixture triethylamine (38 ml) was added and stirred at 37 °C. After that, the reaction mixture was allowed to stand at room temperature for 1 hour. The solvent was again removed by evaporation under reduced pressure and ice water (300 mL) was added to the residue. The pH of the mixture was adjusted to 2 using concentrated hydrochloric acid, at which point crystals were precipitated, and the precipitated crystals were collected by filtration and washed with water. Finally, the target compound F3 was purified by recrystallization from ethyl acetate to give the target compound F3 (17.5 g, 88% yield) as colorless needle-like crystals.

[1] Patent: WO2011/20615, 2011, A1. Location in patent: Page/Page column 75; 76
[2] Journal of Medicinal Chemistry, 2008, vol. 51, # 12, p. 3357 - 3359
[3] Patent: US2015/175560, 2015, A1. Location in patent: Paragraph 0468; 0470