Dichloromethane → 5-{4-[(4S,5R)-3-(dichloroacetyl)-4-(fluoromethyl)-2,2-dimethyl-1,3-oxazolidin-5-yl]phenyl}-2-(3-fluorooxetan-3-yl)pyridine

Participants

Reaction Conditions

Reaction Steps

To a degassed solution of the product of step 1, Example 17 (300.0 mg, 1.29 mmol), bis(pinacolato)diboron (354 mg, 1.39 mmol), and potassium acetate (342 mg, 3.48 mmol) in 1,4-dioxane (4.65 mL) is added [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (81.2 mg, 0.099 mmol) and the reaction mixture is heated at 80-90° C. After 3 hours (4S,5R)-3-(dichloroacetyl)-4-(fluoromethyl)-5-(4-iodophenyl)-2,2-dimethyl-1,3-oxazolidine (see WO2013057619, 444 mg, 0.994 mmol) is added to the reaction mixture followed by a degassed solution of sodium carbonate (422 mg, 3.98 mmol) in water (2.5 mL). The reaction mixture is heated at 80-90° C. for 4 hours before being cooled to room temperature, diluted with ethyl acetate, and washed with water, then brine, dried, and concentrated. The residue is purified by chromatography on silica gel eluting with a gradient of 0-30% EtOAc in hexanes to afford the title compound (380 mg): MS (ESI+) m/z of 471.1/473.0 [M+H].

Provenance & Evidence