Pinacol → 4-chloro-3-(4-fluoro-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine

Participants

Reaction Conditions

Reaction Steps

580 mg (13.69 mmol) of vacuum dried anhydrous lithium chloride was dissolved in 30 mL of anhydrous THF under nitrogen. The mixture was cooled to 0° C. and 1.5 mL (3.0 mmol) of a 2 M solution of iso-propylmagnesium chloride in anhydrous THF was added. To this mixture was added at 0° C. a solution of 1.064 g (2.33 mmol) of 5-bromo-4-chloro-3-(4-fluoro-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine in 20 mL of anhydrous THF under nitrogen. The resulting mixture was stirred at 0° C. for 2 h before 1.0 mL (4.3 mmol) of tri-iso-propylborate was added at 0° C. The resulting mixture was allowed to stir at that temperature for 2.5 h. 990 mg (8.38 mmol) of pinacol was added and the mixture stirred for 24 h, allowing to warm to room temperature. The resulting reaction mixture was distributed between diethyl ether and a saturated aqueous solution of ammonium chloride. The organic phase was separated, dried over sodium sulfate and evaporated. The residue was purified by flash chromatography on silica gel using a gradient of ethyl acetate and hexanes to afford 569 mg (1.13 mmol, 48%) of 4-chloro-3-(4-fluoro-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine as a beige solid. 1H-NMR [500 MHz, d6-DMSO] δ: 8.46 (s, 1H), 7.83 (s, 1H), 7.50 (dd (m), 2H), 7.27 (t (m), 2H), 5.68 (s, 2H), 3.57 (t, 2H), 1.32 (s, 12H), −0.09 (s, 9H); MS [MH+] m/z: 503

Provenance & Evidence