Thionyl Chloride → 3-{3'-Chloro-4'-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-biphenyl-4-yl}-propionic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

Trifluoromethanesulfonic acid 3-chloro-4-[2-(2-chloro-pyridin-4-yl)-3,3,3-trifluoro-2-hydroxy-1-methyl-propyl]-phenyl ester (Example 26, Step 1, 100 mg, 0.2 mmol), 4-(2-methoxycarbonylethyl)phenyl boronic acid (53 mg, 0.24 mmol) and chloro-{2′-(dimethylamino)-2-biphenylyl}-(dinorbornylphosphin)-palladium (3 mg, 0.005 mmol) in dioxane (0.8 ml) was treated with water (0.22 ml) and K3PO4 (128 mg, 0.6 mmol) and stirred at 100° C. under argon for 3 h. To reaction mixture were added dioxane (0.5 ml), water (0.022 ml) and chloro-{2′-(dimethylamino)-2-biphenyl}-(dinorbornylphosphin)-palladium (2 mg). The mixture was stirred at 100° C. under argon for 6 h. The reaction mixture was cooled down to r.t., diluted with ethyl acetate, washed with water and brine, dried over MgSO4 and concentrated in vacuo. The crude product was dissolved in methanol (2 ml) and treated with thionylchloride (56 mg, 0.5 mmol) at 0° C. The reaction solution was stirred at r.t. for 5 h. The mixture was poured on ice-water and sat aq NaHCO3, extracted twice with AcOEt. The combined organic phases were washed with sat aq NaCl, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (10 g silica gel, heptane/AcOEt 3:1) to give the title compound as colorless

Provenance & Evidence