1-BROMO-5-DIFLUOROMETHYL-2-FLUOROBENZENE synthesis

Yield:1142228-23-6 65%

Reaction Conditions:

with anhydrous potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II) dichloromethane adduct in 1,4-dioxane at 90; for 18 h;Inert atmosphere;

Steps:

T26

2-(5-(Difluoromethyl)-2-fluorophenyl)-4,4,5,5-tetramethyl-1,3,2- dioxaborolane (T26.1). A stirred mixture of l-bromo-5-difluoromethyl-2-fluorobenzene (commercially available from Oakwood Products, Inc.) (2.0231 g, 8.991 mmol), bis(pinacolato)diboron (2.5123 g, 9.893 mmol), dichloro[l,l'- bis(diphenylphosphino)ferrocene]palladium (II) DCM adduct (0.3688 g, 0.4516 mmol), and potassium acetate (2.6504 g, 27.01 mmol) in dry 1,4-dioxane (35 mL) was purged with argon and placed under vacuum and the purging vacuum process repeated three times. The mixture was heated to 90°C and monitored with LC-MS and TLC. After 18 hours, the reaction was cooled to room temperature and then filtered through C₆lite filter aid. The organic solvent was removed under reduced pressure, and the residue was purified on a 40 g column of silica gel (0-10% EtOAc in hexanes) to afford T26.1 as a colorless oil that was used without further purification (1.6019 g, 65% yield). ¹H NMR (400 MHz, CDCl₃) δ ppm 7.89 (1 H, td, J=2.7, 1.2 Hz), 7.63 (1 H, m), 7.09 (1 H, t, J=8.6 Hz), 6.62 (1H, t), 1.35 (12 H, s).

References:

WO2009/111056,2009,A1 Location in patent:Page/Page column 233