Ethyl Acetate → 6-([1,1'-biphenyl]-4-yl)-2-(((3R,3aR,6R,6aS)-6-((tert-butyldimethylsilyl)oxy)hexahydrofuro[3,2-b]furan-3-yl)oxy)-3-((2-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[4,5-c]pyridine

Participants

Reaction Conditions

Reaction Steps

Palladium tetrakistriphenylphosphine (42.6 mg, 0.037 mmol) was added to a stirred suspension of 2-(((3R,3aR,6R,6aS)-6-((tert-butyldimethylsilyl)oxy)hexahydrofuro[3,2-b]furan-3-yl)oxy)-6-chloro-3-((2-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[4,5-c]pyridine (Intermediate 46, 100.0 mg, 0.184 mmol), 4-biphenylboronic acid (54.8 mg, 0.277 mmol), and potassium phosphate tribasic (117.0 mg, 0.553 mmol) in degassed 20% water in dioxane (1.44 mL). The reaction mixture stirred under N2 at 85° C. After 2 h, more palladium tetrakistriphenylphosphine (42.6 mg, 0.037 mmol) was added. The reaction mixture heated under N2 at 85° C. for another 7 h, then cooled to room temperature and the lower aqueous layer was drawn off and discarded. The remaining reaction mixture was added to EtOAc (50 mL), filtered, and the resulting solids were washed with EtOAc (2×15 mL). The filtrate was evaporated under reduced pressure. Flash chromatography of the resulting residue utilizing a 24 g silica RediSep Rf® Gold column and employing a 0-100% EtOAc/hexane gradient afforded the title compound. LC-MS: calculated for C36H49N3O5Si2 659.32 observed m/e: 660.13 (M+H)+ (Rt 1.58/2.0 min).

Provenance & Evidence