Synthesis of 2-(2,6-difluoro-4-methylphenyl)-4,4,5,5-tetramethyl-l ,3,2-dioxaboroane To a solution of 1 ,3-difluoro-5-methylbenzene (1.Oeq) in dry THF(0.2M) under an atmosphere of N2 at -78°C was added n-butyllithium (leq, 1.6M in hexanes) slowly keeping the internal temperature below -65°C. The reaction was stirred for 2 hrs at -78°C, followed by the addition of 2-isopropoxy-4,4,5,5-tetramethyl-l,3,2- dioxaborolane (1.15eq). The reaction was allowed to warm to room temperature. Upon completion, the reaction was quenched with NaHC03 (sat.) and extracted with EtOAc. The organics were washed with brine, dried over Na2S04, filtered and concentrated to yield 2-(2,6-difluoro-4-methylphenyl)-4,4,5,5-tetramethyl-l,3,2-dioxaboroane as a white solid in 92%. 1H NMR (400 MHz, ) δ ppm 6.67 (dd, J=9.39, 0.78 Hz, 2 H), 2.34 (s, 3 H), 1.38 (s, 12 H).【WO2012/4217, 2012, A1】
2-(4-Methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (5): n-BuLi (2M in hexane, 21.4 mL, 3.39 g, 53.0 mmol) was added within 25 min at ‒78 °C to a solution of 4-bromoanisole (4, 3.30 mL, 4.95 g, 26.5 mmol) in anhydrous THF (120 mL). The mixture was stirred at ‒78 °C for 1.5 h, 2-isopropoxy-4,4,5,5-tetramethyl1,3,2-dioxaborolane (11.0 mL, 10.0 g, 53.8 mmol) was added and the temperature was raised to rt overnight. The mixture was brought to pH ~7 by addition of 1N HCl. EtOAc (100 mL) and brine were added and the layers were separated. The aqueous layer was extracted with EtOAc (2×100 mL). The combined organic layers were washed with brine, dried (Na2SO4) and concentrated at reduced pressure to yield the product as a colorless oil (5.96 g, 25.5 mmol, 95%). The NMR-spectroscopic data were in agreement with published data: 3 1 H NMR (300 MHz, CDCl3): δ=1.33 (s, 12H, 4×CCH3), 3.82 (s, 3H, OMe), 6.90 (m, 2H, 3ʼ-H, 5ʼ-H), 7.76 ppm (m, 2H, 2ʼ-H, 4ʼ-H).【European Journal of Organic Chemistry, 2019, 6697 - 6701】
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