2-(4-bromo-2-methoxyphenyl)propan-2-ol

Conditions: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-(4-bromo-2-methoxyphenyl)propan-2-ol (50.0 mg, 0.20 mmol) in toluene (0.81 mL) was added methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylate (72 mg, 0.22 mmol), ethanol (0.43 mL), and tetrahydrofuran (0.43 mL). This was followed by the addition of 2M potassium carbonate aqueous (0.58 mL, 1.2 mmol). The reaction was evacuated and back filled with nitrogen (3×) then Pd(dppf)Cl2 (19.0 mg, 0.023 mmol) was added and the reaction heated to 115° C. for 3 hours. The reaction was then cooled to room temperature and filtered through a pad of celite washing with ethyl acetate. The filtrate was concentrated under reduced pressure and purified via column chromatography (0-40% ethyl acetate/heptanes) to provide the title compound (45 mg, 59% yield) as a solid. The reaction was evacuated back filled with nitrogen (3×) The reaction was then cooled to room temperature filtered through a pad of celite washing with ethyl acetate The filtrate was concentrated under reduced pressure purified via column chromatography (0-40% ethyl acetate/heptanes)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-bromo-2-iodoanisole (668 mg, 2.14 mmol) and acetone (0.471 mL, 6.40 mmol) in tetrahydrofuran (7.62 mL) at −78° C. was added n-BuLi (2.5M in hexane, 0.940 mL, 2.35 mmol) in a dropwise manner. The reaction mixture was stirred at −78° C. for 2 hours. The reaction mixture was quenched with saturated aqueous ammonium chloride, warmed to room temperature and extracted with ethyl acetate (2×). The combined organic layers were dried over magnesium sulfate and filtered, and concentrated under reduced pressure yielding 680 mg of crude oil. Purification by column chromatography (0-10% ethyl acetate/heptanes) afforded the title compound (133 mg, 25% yield) as a clear, colorless oil. MS (ES+) 226.9 (M−H2O+H)+. 1H NMR (400 MHz, CDCl3) δ: 7.20 (d, 1H), 7.06-7.10 (m, 1H), 7.04 (d, 1H), 3.91 (s, 3H), 1.58 (s, 6H). The reaction mixture was quenched with saturated aqueous ammonium chloride warmed to room temperature extracted with ethyl acetate (2×) The combined organic layers were dried over magnesium sulfate filtered concentrated under reduced pressure yielding 680 mg of crude oil Purification by column chromatography (0-10% ethyl acetate/heptanes)

Conditions: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-(4-bromo-2-methoxyphenyl)propan-2-ol (50.0 mg, 0.20 mmol) in toluene (0.81 mL) was added methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylate (72 mg, 0.22 mmol), ethanol (0.43 mL), and tetrahydrofuran (0.43 mL). This was followed by the addition of 2M potassium carbonate aqueous (0.58 mL, 1.2 mmol). The reaction was evacuated and back filled with nitrogen (3×) then Pd(dppf)Cl2 (19.0 mg, 0.023 mmol) was added and the reaction heated to 115° C. for 3 hours. The reaction was then cooled to room temperature and filtered through a pad of celite washing with ethyl acetate. The filtrate was concentrated under reduced pressure and purified via column chromatography (0-40% ethyl acetate/heptanes) to provide the title compound (45 mg, 59% yield) as a solid. The reaction was evacuated back filled with nitrogen (3×) The reaction was then cooled to room temperature filtered through a pad of celite washing with ethyl acetate The filtrate was concentrated under reduced pressure purified via column chromatography (0-40% ethyl acetate/heptanes)

Conditions: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-(4-bromo-2-methoxyphenyl)propan-2-ol (50.0 mg, 0.20 mmol) in toluene (0.81 mL) was added methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylate (72 mg, 0.22 mmol), ethanol (0.43 mL), and tetrahydrofuran (0.43 mL). This was followed by the addition of 2M potassium carbonate aqueous (0.58 mL, 1.2 mmol). The reaction was evacuated and back filled with nitrogen (3×) then Pd(dppf)Cl2 (19.0 mg, 0.023 mmol) was added and the reaction heated to 115° C. for 3 hours. The reaction was then cooled to room temperature and filtered through a pad of celite washing with ethyl acetate. The filtrate was concentrated under reduced pressure and purified via column chromatography (0-40% ethyl acetate/heptanes) to provide the title compound (45 mg, 59% yield) as a solid. The reaction was evacuated back filled with nitrogen (3×) The reaction was then cooled to room temperature filtered through a pad of celite washing with ethyl acetate The filtrate was concentrated under reduced pressure purified via column chromatography (0-40% ethyl acetate/heptanes)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-bromo-2-iodoanisole (668 mg, 2.14 mmol) and acetone (0.471 mL, 6.40 mmol) in tetrahydrofuran (7.62 mL) at −78° C. was added n-BuLi (2.5M in hexane, 0.940 mL, 2.35 mmol) in a dropwise manner. The reaction mixture was stirred at −78° C. for 2 hours. The reaction mixture was quenched with saturated aqueous ammonium chloride, warmed to room temperature and extracted with ethyl acetate (2×). The combined organic layers were dried over magnesium sulfate and filtered, and concentrated under reduced pressure yielding 680 mg of crude oil. Purification by column chromatography (0-10% ethyl acetate/heptanes) afforded the title compound (133 mg, 25% yield) as a clear, colorless oil. MS (ES+) 226.9 (M−H2O+H)+. 1H NMR (400 MHz, CDCl3) δ: 7.20 (d, 1H), 7.06-7.10 (m, 1H), 7.04 (d, 1H), 3.91 (s, 3H), 1.58 (s, 6H). The reaction mixture was quenched with saturated aqueous ammonium chloride warmed to room temperature extracted with ethyl acetate (2×) The combined organic layers were dried over magnesium sulfate filtered concentrated under reduced pressure yielding 680 mg of crude oil Purification by column chromatography (0-10% ethyl acetate/heptanes)

Conditions: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-(4-bromo-2-methoxyphenyl)propan-2-ol (50.0 mg, 0.20 mmol) in toluene (0.81 mL) was added methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylate (72 mg, 0.22 mmol), ethanol (0.43 mL), and tetrahydrofuran (0.43 mL). This was followed by the addition of 2M potassium carbonate aqueous (0.58 mL, 1.2 mmol). The reaction was evacuated and back filled with nitrogen (3×) then Pd(dppf)Cl2 (19.0 mg, 0.023 mmol) was added and the reaction heated to 115° C. for 3 hours. The reaction was then cooled to room temperature and filtered through a pad of celite washing with ethyl acetate. The filtrate was concentrated under reduced pressure and purified via column chromatography (0-40% ethyl acetate/heptanes) to provide the title compound (45 mg, 59% yield) as a solid. The reaction was evacuated back filled with nitrogen (3×) The reaction was then cooled to room temperature filtered through a pad of celite washing with ethyl acetate The filtrate was concentrated under reduced pressure purified via column chromatography (0-40% ethyl acetate/heptanes)

Conditions: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-(4-bromo-2-methoxyphenyl)propan-2-ol (50.0 mg, 0.20 mmol) in toluene (0.81 mL) was added methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylate (72 mg, 0.22 mmol), ethanol (0.43 mL), and tetrahydrofuran (0.43 mL). This was followed by the addition of 2M potassium carbonate aqueous (0.58 mL, 1.2 mmol). The reaction was evacuated and back filled with nitrogen (3×) then Pd(dppf)Cl2 (19.0 mg, 0.023 mmol) was added and the reaction heated to 115° C. for 3 hours. The reaction was then cooled to room temperature and filtered through a pad of celite washing with ethyl acetate. The filtrate was concentrated under reduced pressure and purified via column chromatography (0-40% ethyl acetate/heptanes) to provide the title compound (45 mg, 59% yield) as a solid. The reaction was evacuated back filled with nitrogen (3×) The reaction was then cooled to room temperature filtered through a pad of celite washing with ethyl acetate The filtrate was concentrated under reduced pressure purified via column chromatography (0-40% ethyl acetate/heptanes)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-bromo-2-iodoanisole (668 mg, 2.14 mmol) and acetone (0.471 mL, 6.40 mmol) in tetrahydrofuran (7.62 mL) at −78° C. was added n-BuLi (2.5M in hexane, 0.940 mL, 2.35 mmol) in a dropwise manner. The reaction mixture was stirred at −78° C. for 2 hours. The reaction mixture was quenched with saturated aqueous ammonium chloride, warmed to room temperature and extracted with ethyl acetate (2×). The combined organic layers were dried over magnesium sulfate and filtered, and concentrated under reduced pressure yielding 680 mg of crude oil. Purification by column chromatography (0-10% ethyl acetate/heptanes) afforded the title compound (133 mg, 25% yield) as a clear, colorless oil. MS (ES+) 226.9 (M−H2O+H)+. 1H NMR (400 MHz, CDCl3) δ: 7.20 (d, 1H), 7.06-7.10 (m, 1H), 7.04 (d, 1H), 3.91 (s, 3H), 1.58 (s, 6H). The reaction mixture was quenched with saturated aqueous ammonium chloride warmed to room temperature extracted with ethyl acetate (2×) The combined organic layers were dried over magnesium sulfate filtered concentrated under reduced pressure yielding 680 mg of crude oil Purification by column chromatography (0-10% ethyl acetate/heptanes)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-bromo-2-iodoanisole (668 mg, 2.14 mmol) and acetone (0.471 mL, 6.40 mmol) in tetrahydrofuran (7.62 mL) at −78° C. was added n-BuLi (2.5M in hexane, 0.940 mL, 2.35 mmol) in a dropwise manner. The reaction mixture was stirred at −78° C. for 2 hours. The reaction mixture was quenched with saturated aqueous ammonium chloride, warmed to room temperature and extracted with ethyl acetate (2×). The combined organic layers were dried over magnesium sulfate and filtered, and concentrated under reduced pressure yielding 680 mg of crude oil. Purification by column chromatography (0-10% ethyl acetate/heptanes) afforded the title compound (133 mg, 25% yield) as a clear, colorless oil. MS (ES+) 226.9 (M−H2O+H)+. 1H NMR (400 MHz, CDCl3) δ: 7.20 (d, 1H), 7.06-7.10 (m, 1H), 7.04 (d, 1H), 3.91 (s, 3H), 1.58 (s, 6H). The reaction mixture was quenched with saturated aqueous ammonium chloride warmed to room temperature extracted with ethyl acetate (2×) The combined organic layers were dried over magnesium sulfate filtered concentrated under reduced pressure yielding 680 mg of crude oil Purification by column chromatography (0-10% ethyl acetate/heptanes)

Conditions: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-(4-bromo-2-methoxyphenyl)propan-2-ol (50.0 mg, 0.20 mmol) in toluene (0.81 mL) was added methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylate (72 mg, 0.22 mmol), ethanol (0.43 mL), and tetrahydrofuran (0.43 mL). This was followed by the addition of 2M potassium carbonate aqueous (0.58 mL, 1.2 mmol). The reaction was evacuated and back filled with nitrogen (3×) then Pd(dppf)Cl2 (19.0 mg, 0.023 mmol) was added and the reaction heated to 115° C. for 3 hours. The reaction was then cooled to room temperature and filtered through a pad of celite washing with ethyl acetate. The filtrate was concentrated under reduced pressure and purified via column chromatography (0-40% ethyl acetate/heptanes) to provide the title compound (45 mg, 59% yield) as a solid. The reaction was evacuated back filled with nitrogen (3×) The reaction was then cooled to room temperature filtered through a pad of celite washing with ethyl acetate The filtrate was concentrated under reduced pressure purified via column chromatography (0-40% ethyl acetate/heptanes)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-bromo-2-iodoanisole (668 mg, 2.14 mmol) and acetone (0.471 mL, 6.40 mmol) in tetrahydrofuran (7.62 mL) at −78° C. was added n-BuLi (2.5M in hexane, 0.940 mL, 2.35 mmol) in a dropwise manner. The reaction mixture was stirred at −78° C. for 2 hours. The reaction mixture was quenched with saturated aqueous ammonium chloride, warmed to room temperature and extracted with ethyl acetate (2×). The combined organic layers were dried over magnesium sulfate and filtered, and concentrated under reduced pressure yielding 680 mg of crude oil. Purification by column chromatography (0-10% ethyl acetate/heptanes) afforded the title compound (133 mg, 25% yield) as a clear, colorless oil. MS (ES+) 226.9 (M−H2O+H)+. 1H NMR (400 MHz, CDCl3) δ: 7.20 (d, 1H), 7.06-7.10 (m, 1H), 7.04 (d, 1H), 3.91 (s, 3H), 1.58 (s, 6H). The reaction mixture was quenched with saturated aqueous ammonium chloride warmed to room temperature extracted with ethyl acetate (2×) The combined organic layers were dried over magnesium sulfate filtered concentrated under reduced pressure yielding 680 mg of crude oil Purification by column chromatography (0-10% ethyl acetate/heptanes)

Conditions: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-(4-bromo-2-methoxyphenyl)propan-2-ol (50.0 mg, 0.20 mmol) in toluene (0.81 mL) was added methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylate (72 mg, 0.22 mmol), ethanol (0.43 mL), and tetrahydrofuran (0.43 mL). This was followed by the addition of 2M potassium carbonate aqueous (0.58 mL, 1.2 mmol). The reaction was evacuated and back filled with nitrogen (3×) then Pd(dppf)Cl2 (19.0 mg, 0.023 mmol) was added and the reaction heated to 115° C. for 3 hours. The reaction was then cooled to room temperature and filtered through a pad of celite washing with ethyl acetate. The filtrate was concentrated under reduced pressure and purified via column chromatography (0-40% ethyl acetate/heptanes) to provide the title compound (45 mg, 59% yield) as a solid. The reaction was evacuated back filled with nitrogen (3×) The reaction was then cooled to room temperature filtered through a pad of celite washing with ethyl acetate The filtrate was concentrated under reduced pressure purified via column chromatography (0-40% ethyl acetate/heptanes)