Lithium Hydroxide → 4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-1-(2-trimethylsilylethoxymethyl)-imidazo[4,5-b]pyridin-5-yl]benzonitrile

Participants

Reaction Conditions

Reaction Steps

LiOH (0.43 ml, 1.290 mmol) and 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (43.2 mg, 0.053 mmol) were added to a stirred solution of (3R,3aR,6R,6aR)-6-[6-chloro-5-iodo-1-(2-trimethylsilylethoxy-methyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol (284.9 mg, 0.514 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (143.1 mg, 0.625 mmol) in dioxane (4.2 ml) and water (0.60 ml). The reaction mixture was degassed (3×) and placed under nitrogen before being heated to 80° C. for 1.5 hours. Then the reaction mixture was cooled and partitioned between EtOAc (50 ml) and water (50 mL). The aqueous layer was extracted with EtOAc (2×50 ml). The organic layers were combined, washed with brine (1×50 ml), dried over Na2SO4′ filtered, and evaporated under reduced pressure to give an amber residue. Flash chromatography of the residue utilizing a 12 g silica RediSep Rf® column and employing a 0-60% EtOAc/hexane gradient followed by 60% EtOAc/hexane afforded the title compound as a yellow residue. LC-MS: calculated for C25H29ClN4O5Si 528.16 observed m/e: 529.22 (M+H)+ (Rt 2.34/4 min).

Provenance & Evidence