Potassium Carbonate → 5-(3'-Chloro-6-difluoromethoxy-biphenyl-3-ylmethyl)-pyridine-2-carboxylic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

In a 40 mL vial equipped with a stir bar was placed carbonic acid 3′-chloro-6-difluoromethoxy-biphenyl-3-ylmethyl ester methyl ester (I-151, 700 mg, 2.04 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridine-2-carboxylicacid methyl ester (590 mg, 2.24 mmol), potassium carbonate (846 mg, 6.12 mmol), 1,5-bis(diphenylphosphino)pentane (270 mg, 0.612 mmol) and DMF (10 mL). The reaction mixture was degassed for 15 minutes by bubbling nitrogen and then allylpalladium(II) chloride dimer (112 mg, 0.306 mmol) was added. The reaction mixture was heated to 85° C. for 4 hours. To the reaction mixture was added water (40 mL) and ethyl acetate (40 mL) and the mixture was filtered through Celite. The layers of the filtrate were separated and the aqueous portion was extracted with ethyl acetate (40 mL). The organic portions were combined, washed with brine (40 mL), dried (MgSO4) and concentrated. The crude material was purified by a 50 gram silica gel SNAP cartridge (Biotage SP4 Flash Chromatography instrument) utilizing gradient elution of 12-100% ethyl acetate/hexanes to produce 458 mg of I-152 as a viscous yellow solid in 56% yield.

Provenance & Evidence