1,4-Bis(diphenylphosphino)butane → [(3R,3aR,6R,6aS)-3-[[6-chloro-5-(4-pyrrolidin-1-ylphenyl)-1H-imidazo[4,5-b]pyridin-2-yl]oxy]-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy-tert-butyl-dimethyl-silane

Participants

Reaction Steps

1,4-bis(diphenylphosphino)butane (5.9 mg, 0.014 mmol), palladium(II) acetate (4.0 mg, 0.018 mmol), and ethanol (0.17 ml) were combined in a 4 ml vial. The catalyst mixture was degassed (3×) and placed under nitrogen. The catalyst mixture was an amber suspension that was stirred at room temperature. Sodium borohydride (19.0 mg, 0.502 mmol) was added to a stirred solution of [(3R,3aR,6R,6aS)-3-[1-allyl-6-chloro-5-(4-pyrrolidin-1-ylphenyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy-tert-butyl-dimethyl-silane (50.3 mg, 0.084 mmol) in ethanol (0.67 ml). The reaction mixture was a yellow suspension that was degassed (3×) and placed under nitrogen. After being stirred at room temperature for 40 minutes, the catalyst mixture was transferred to the reaction mixture via syringe. The reaction mixture was degassed (2×) and placed under nitrogen. After 3.5 hours, the reaction mixture was filtered and evaporated under reduced pressure. The resulting residue was purified by preparative HPLC reverse phase (C-18), using a 30×150 mm Sunfire™ column and eluting (20 ml/min) with a 14 minute 20%-100% acetonitrile/water+0.05% TFA gradient followed by a 5 minute 100% acetonitrile+0.05% TFA flush. The product fractions were combined, frozen, and lyophilized to give the title compound as a yellow solid. LC-MS: calculated for C28H37ClN4O4Si 556.23 observed m/e: 557.29 (M+H)+ (Rt 1.24/2 min).

Provenance & Evidence