The general procedure for the synthesis of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indol-2-one from 4-bromoindolone and pinacol bis(boronic acid) ester is as follows:
1. in a dry reaction vial, 4-bromodihydroindol-2-one (1.038 g, 4.90 mmol), pinacol ester of bisboronic acid (1.903 g, 7.49 mmol), [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride complexed with dichloromethane (0.601 g, 0.73 mmol) and potassium acetate (1.480 g , 15.08 mmol) in a solution of 1,4-dioxane (30 mL).
2. The reaction mixture was stirred at 110 °C for 2 hours.
3. After completion of the reaction, the mixture was cooled to room temperature and filtered through a cartridge containing 10 g of diatomaceous earth.
4. The filter cake was washed with ethyl acetate (3 x 30 mL), the filtrates were combined and concentrated under vacuum to give a brown liquid.
5. The crude product was dissolved in dichloromethane (about 10 mL) and purified by passing through a 100 g SNAP silica gel column using a Biotage SP4 semi-automated fast column chromatography system eluting with a gradient of 20% to 50% ethyl acetate in cyclohexane solution.
6. Fractions containing the target product were collected, combined and concentrated under vacuum.
7. The concentrate was dissolved in dichloromethane (~10 mL), transferred to a pre-weighed vial and the solvent was evaporated under a stream of nitrogen.
8. The residue was ground with ether (5 x 5 mL) and the supernatant was precipitated by decantation each time and finally dried under vacuum under a stream of nitrogen to afford the milky white solid product 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)dihydroindol-2-one (941.8 mg, 3.63 mmol, 74% yield).
Product characterization: LCMS (2 min form): retention time Rt = 0.93 min, [MH]+ = 260.3.
