2,4,5-Trifluorophenylboronic acid

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 7-(methoxycarbonyl)-8-{[(trifluoromethyl)sulfonyl]oxy}-4-oxa-1-oxoniaspiro[4.5]dec-7-ene (5.65 g, 16.0 mmol) dissolved in N,N-dimethylformamide (190 mL) were added aqueous sodium carbonate solution (2.0M, 20 mL, 39.0 mmol) and 2,4,5-trifluorophenylboronic acid (4.11 g, 23.4 mmol). The resulting mixture was degassed and treated with PdCl2(dppf) ([1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II), complex with dichloromethane (1:1), 1274 mg). The resulting mixture was stirred under a nitrogen atmosphere at room temperature overnight, filtered over Celite, diluted with ethyl acetate and washed with water. The organic phase was dried over anhydrous sodium sulfate, evaporated and the crude product was purified by chromatography on a Biotage® system (silica gel, ethyl acetate in hexanes gradient 30-50%) to yield the title compound. The resulting mixture was degassed treated with PdCl2(dppf) ([1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II), complex with dichloromethane (1:1), 1274 mg) filtered over Celite diluted with ethyl acetate washed with water The organic phase was dried over anhydrous sodium sulfate evaporated the crude product was purified by chromatography on a Biotage® system (silica gel, ethyl acetate in hexanes gradient 30-50%)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,4,5-trifluorophenylboronic acid (43.8 g, 249.2 mmol), 4-iodophenol (50 g, 226.5 mmol), potassium carbonate (78 g, 556.3 mmol), Pd(dppf)Cl2 methylene chloride complex (5.5 g, 6.8 mmol), DMF (150 mL), and water (38 mL) was degassed, purged with nitrogen, and heated at 50° C. overnight. The mixture was then diluted with EtOAc and water, acidified with conc. HCl under cooling with ice-water bath, stirred with charcoal, and filtered through Celite. The organic layer was separated, washed with water and brine, dried over sodium sulfate, filtered, and evaporated to afford a deep red oily crude product. The crude product in EtOAc was passed through silica gel to give 2′,4′,5′-trifluoro-biphenyl-4-ol as a light brown solid (38 g, 75%). LC-MS (ES) calculated for C12H7F3O, 224.18; found m/z 224 [M+H]. was degassed purged with nitrogen The mixture was then diluted with EtOAc and water under cooling with ice-water bath filtered through Celite The organic layer was separated washed with water and brine dried over sodium sulfate filtered evaporated to afford a deep red oily crude product

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,4,5-trifluorophenylboronic acid (43.8 g, 249.2 mmol), 4-iodophenol (50 g, 226.5 mmol), potassium carbonate (78 g, 556.3 mmol), Pd(dppf)Cl2 methylene chloride complex (5.5 g, 6.8 mmol), DMF (150 mL), and water (38 mL) was degassed, purged with nitrogen, and heated at 50° C. overnight. The mixture was then diluted with EtOAc and water, acidified with conc. HCl under cooling with ice-water bath, stirred with charcoal, and filtered through Celite. The organic layer was separated, washed with water and brine, dried over sodium sulfate, filtered, and evaporated to afford a deep red oily crude product. The crude product in EtOAc was passed through silica gel to give 2′,4′,5′-trifluoro-biphenyl-4-ol as a light brown solid (38 g, 75%). LC-MS (ES) calculated for C12H7F3O, 224.18; found m/z 224 [M+H]. was degassed purged with nitrogen The mixture was then diluted with EtOAc and water under cooling with ice-water bath filtered through Celite The organic layer was separated washed with water and brine dried over sodium sulfate filtered evaporated to afford a deep red oily crude product

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl 2-chloroisonicotinate (3.25 g, 18.94 mmol), 2,4,5-trifluorophenylboronic acid (5.00 g, 28.41 mmol), potassium carbonate (3.93 g, 28.41 mmol) and PdCl2 (dppf) (0.411 g, 0.57 mmol) were mixed in methanol (20 mL) in two 20 mL microwave vials. The vials were capped and heated at 100° C. for 10 min in a single node microwave reactor. The reaction mixture was suspended in methanol, filtered and the filtrate evaporated to yield a dark red slurry. DCM and water were added and the phases separated. The water phase (pH 9) was extracted with DCM and the combined organic phase washed with brine, passed through a phase separator and evaporated to yield a brown solid. The crude brown solid was dissolved in MTBE (120 mL) and solids filtered off. Hydrogen chloride (4 M in dioxane, 4.74 mL, 18.94 mmol) was added dropwise and a suspension was formed. The suspension was stirred at room temperature for 45 min. The solid was collected by filtration and washed with MTBE. MTBE and satd NaHCO3 were added. The organic phase was dried over Na2SO4, filtered and evaporated to yield methyl 2-(2,4,5-trifluorophenyl)isonicotinate (1.676 g, 33%) as a beige solid. The MTBE-filtrate was washed with satd NaHCO3, dried over Na2SO4, filtered and evaporated to yield a brown solid. The residue was purified via Biotage (0=>20% EtOAc in heptane, 6 CV; Biotage® KP-SIL 100 g column) to yield methyl 2-(2,4,5-trifluorophenyl)-isonicotinate (0.86 g, 17%) as a white solid. 1H NMR (600 MHz, cdcl3) δ 3.97 (s, 3H), 7.00-7.07 (m, 1H), 7.81 (dd, 1H), 7.90-7.97 (m, 1H), 8.32-8.33 (m, 1H), 8.83 (dd, 1H). MS m/z 268 (M+H)+ The vials were capped filtered the filtrate evaporated to yield a dark red slurry the phases separated The water phase (pH 9) was extracted with DCM the combined organic phase washed with brine evaporated to yield a brown solid solids filtered off a suspension was formed The solid was collected by filtration washed with MTBE were added The organic phase was dried over Na2SO4 filtered evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The compound was prepared according to Example 1 using 2,4,5-trifluorophenylboronic acid and 4,6-dichloropyrimidine. The resultant chloro compound was converted to iodo with hydroiodic acid as described in the general procedure. The compound was prepared

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Bis(tricyclohexylphosphine)palladium (200 mg, 0.3 mmol) was added to a stirred solution of 3-(4-iodo-phenoxymethyl)-benzoic acid methyl ester (3.68 g, 10 mmol), potassium carbonate (2.76 g, 20 mmol) and 2,4,5-trifluorophenylboronic acid (3.5 g, 20 mmol) in 100 mL dioxane and 10 mL H2O were reacted as above and purified by flash chromatography with a gradient of 0-5% ethyl acetate in hexanes to give 2.9 g (77.9%) of 3-(2′,4′,5′-trifluoro-biphenyl-4-yloxymethyl)-benzoic acid methyl ester. were reacted as above and purified by flash chromatography with a gradient of 0-5% ethyl acetate in hexanes

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 7-(methoxycarbonyl)-8-{[(trifluoromethyl)sulfonyl]oxy}-4-oxa-1-oxoniaspiro[4.5]dec-7-ene (5.65 g, 16.0 mmol) dissolved in N,N-dimethylformamide (190 mL) were added aqueous sodium carbonate solution (2.0M, 20 mL, 39.0 mmol) and 2,4,5-trifluorophenylboronic acid (4.11 g, 23.4 mmol). The resulting mixture was degassed and treated with PdCl2(dppf) ([1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II), complex with dichloromethane (1:1), 1274 mg). The resulting mixture was stirred under a nitrogen atmosphere at room temperature overnight, filtered over Celite, diluted with ethyl acetate and washed with water. The organic phase was dried over anhydrous sodium sulfate, evaporated and the crude product was purified by chromatography on a Biotage® system (silica gel, ethyl acetate in hexanes gradient 30-50%) to yield the title compound. The resulting mixture was degassed treated with PdCl2(dppf) ([1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II), complex with dichloromethane (1:1), 1274 mg) filtered over Celite diluted with ethyl acetate washed with water The organic phase was dried over anhydrous sodium sulfate evaporated the crude product was purified by chromatography on a Biotage® system (silica gel, ethyl acetate in hexanes gradient 30-50%)