Synthesis
The general procedure for the synthesis of 4-fluoro-2-methylphenylboronic acid from triisopropyl borate and 2-bromo-5-fluorotoluene was carried out as follows: 2-bromo-5-fluorotoluene (250 g) was dissolved in a solvent mixture of tetrahydrofuran (250 ml) and n-hexane (250 ml) under dry conditions, and cooled to -78 °C. At this temperature, n-butyllithium (991.5 ml) was slowly added dropwise and the reaction temperature was maintained in an ice bath. After the dropwise addition, the reaction mixture was stirred for 1 hour. Subsequently, triisopropyl borate (373.11 g) was added dropwise and stirring was continued at -78°C for 1 hour. After completion of the reaction, the reaction mixture was diluted with aqueous sodium hydroxide solution and then washed with n-heptane. The pH of the aqueous layer was adjusted to 2-3 with hydrochloric acid followed by extraction with ethyl acetate. The organic layers were combined and concentrated under vacuum. The concentrated product was dissolved in ethyl acetate at about 40 °C and n-heptane was added to promote crystallization, resulting in 4-fluoro-2-methylphenylboronic acid. The yield was 61.5% and the HPLC purity was 99.00%.
