Step 3: Dissolve 2-fluoro-5-(ethyl formate)phenylboronic acid pinacol ester in a mixture of a solvent miscible with water (e.g., THF, methanol or acetone) and water. Lithium hydroxide (3.0 equiv) was added and the reaction mixture was stirred at room temperature. The progress of the reaction is monitored by TLC and LCMS until the starting material is essentially consumed (reaction time is typically 6-12 hours). Upon completion of the reaction, the THF was concentrated and separated by extraction with ethyl acetate and water. The organic layer was washed with water and the aqueous phases were combined. The washed aqueous phase is acidified with 2N HCl and extracted again with ethyl acetate. The ethyl acetate extracts were combined, dried with sodium sulfate and concentrated in vacuum to give the crude product. The crude product was sufficiently pure in most cases and could be used directly in the next step of the reaction. Reaction conditions: LiOH (3.0 equiv), THF:H2O (1:1), room temperature, 4 h. Yield 65%. Details of the synthesized compounds are given in Table 12.
