Step 5: In 500 mL of degassed tetrahydrofuran (THF), 27.75 g (55 mmol) of tert-butyl 1-(4-bromophenyl) cyclobutylcarbamate, 23.76 g (93.6 mmol) of pinacol ester of bis(boronic acid), 25 g (255 mmol) of potassium acetate, and 2.08 g (2.55 mmol) of 1,1 '-bis(diphenylphosphino) ferrocene palladium(II) dichloride. The reaction mixture was heated to reflux for 3 h. The color of the reaction mixture was observed to change from dark red to black. Due to incomplete reaction, heating was continued for 2 hours. Upon completion of the reaction, the reaction mixture was poured into 400 mL of water and diluted with 700 mL of ethyl acetate. After stirring for 30 minutes, the organic phase was separated and the aqueous phase was extracted twice more with 400 mL and 200 mL of ethyl acetate, respectively. The organic extracts were combined, washed with 200 mL of brine and dried with sodium sulfate. After evaporation of the solvent, the residue was purified by Biotage chromatography to afford 28.99 g (91.3% yield) of tert-butyl 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclobutylcarbamate.1H NMR (400 MHz, DMSO-d6)δ: 7.51-7.67 (m, 3H), 7.38 (d, 2H), 2.22-2.42 (m, 4H), 1.88-2.02 (m, 1H), 1.63-1.80 (m, 1H), 1.00-1.38 (m, 21H) ppm.
