3-bromo-2-fluorobenzamide

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Pd(OAc)2 (123.6 mg, 0.55 mmol), PPh3 (557.5 mg, 2.2 mmol), K2CO3 (3.8 g, 27.5 mmol) and 3-bromo-2-fluorobenzamide (4.0 g, 18.4 mmol) were suspended in 1,4-dioxane (30 mL). After the mixture was heated to 80° C. for 15 min, [3-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)phenyl]boronic acid (5.9 g, 22.0 mmol) was added. Then the reaction mixture was stirred over night at 100° C. After cooling to room temperature, the solvent was removed under reduced pressure. The residue was dissolved in CH2Cl2 (50 mL), then was washed with water (20 mL), brine (20 mL), and dried over Na2SO4. After the solvent was removed, the crude product was purified on an Al2O3 column chomatography, eluting with CH2Cl2/CH3OH (300:1). 3′-({[(1,1-Dimethylethyl)(dimethyl)silyl]oxy}methyl)-2-fluoro-3-biphenylcarboxamide, was obtained (4.1 g, yield: 63%). 1H NMR (400 MHz, CDCl3) δ 0.12 (s, 6H), 0.95 (s, 9H), 4.81 (s, 2H), 7.25-8.12 (m, 7H). After cooling to room temperature the solvent was removed under reduced pressure The residue was dissolved in CH2Cl2 (50 mL) was washed with water (20 mL), brine (20 mL) dried over Na2SO4 After the solvent was removed the crude product was purified on an Al2O3 column chomatography eluting with CH2Cl2/CH3OH (300:1)

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Pd(OAc)2 (123.6 mg, 0.55 mmol), PPh3 (557.5 mg, 2.2 mmol), K2CO3 (3.8 g, 27.5 mmol) and 3-bromo-2-fluorobenzamide (4.0 g, 18.4 mmol) were suspended in 1,4-dioxane (30 mL). After the mixture was heated to 80° C. for 15 min, [3-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)phenyl]boronic acid (5.9 g, 22.0 mmol) was added. Then the reaction mixture was stirred over night at 100° C. After cooling to room temperature, the solvent was removed under reduced pressure. The residue was dissolved in CH2Cl2 (50 mL), then was washed with water (20 mL), brine (20 mL), and dried over Na2SO4. After the solvent was removed, the crude product was purified on an Al2O3 column chomatography, eluting with CH2Cl2/CH3OH (300:1). 3′-({[(1,1-Dimethylethyl)(dimethyl)silyl]oxy}methyl)-2-fluoro-3-biphenylcarboxamide, was obtained (4.1 g, yield: 63%). 1H NMR (400 MHz, CDCl3) δ 0.12 (s, 6H), 0.95 (s, 9H), 4.81 (s, 2H), 7.25-8.12 (m, 7H). After cooling to room temperature the solvent was removed under reduced pressure The residue was dissolved in CH2Cl2 (50 mL) was washed with water (20 mL), brine (20 mL) dried over Na2SO4 After the solvent was removed the crude product was purified on an Al2O3 column chomatography eluting with CH2Cl2/CH3OH (300:1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-bromo-2-fluorobenzamide (3.0 g, 13.76 mmol) in THF (50 mL) was added BH3.Me2S (1.57 mL, 20.6 mmol) and the mixture was stirred at 50° C. for 2 h (monitored by TLC). The reaction was quenched by adding HCl (20 mL, 3 N) after which the result mixture was stirred for 2 h and then THF was removed under vacuum. The aqueous layer was extracted with AcOEt (30 mL), and then was adjusted to pH=9.0 with NaOH (1 N). Then the aqueous layer was extracted with AcOEt (50 mL×2). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated to give 1.30 g of the title compound as a colorless oil (yield: 46%). 1H NMR (400 MHz, D2O) δ 4.30 (S, 2H), 7.19-7.22 (m, 1H), 7.47 (t, J=8.8 Hz, 1H), 7.73-7.77 (m, 1H); 13C NMR (100 MHz, D2O) δ 37.4, 108.9, 121.2, 126.2, 130.7, 135.1, 156.2, 158.6. The reaction was quenched by adding HCl (20 mL, 3 N) after which the result mixture THF was removed under vacuum The aqueous layer was extracted with AcOEt (30 mL) Then the aqueous layer was extracted with AcOEt (50 mL×2) The combined organic layers were washed with brine dried over Na2SO4 filtered concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-bromo-2-fluorobenzamide (3.0 g, 13.76 mmol) in THF (50 mL) was added BH3.Me2S (1.57 mL, 20.6 mmol) and the mixture was stirred at 50° C. for 2 h (monitored by TLC). The reaction was quenched by adding HCl (20 mL, 3 N) after which the result mixture was stirred for 2 h and then THF was removed under vacuum. The aqueous layer was extracted with AcOEt (30 mL), and then was adjusted to pH=9.0 with NaOH (1 N). Then the aqueous layer was extracted with AcOEt (50 mL×2). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated to give 1.30 g of the title compound as a colorless oil (yield: 46%). 1H NMR (400 MHz, D2O) δ 4.30 (S, 2H), 7.19-7.22 (m, 1H), 7.47 (t, J=8.8 Hz, 1H), 7.73-7.77 (m, 1H); 13C NMR (100 MHz, D2O) δ 37.4, 108.9, 121.2, 126.2, 130.7, 135.1, 156.2, 158.6. The reaction was quenched by adding HCl (20 mL, 3 N) after which the result mixture THF was removed under vacuum The aqueous layer was extracted with AcOEt (30 mL) Then the aqueous layer was extracted with AcOEt (50 mL×2) The combined organic layers were washed with brine dried over Na2SO4 filtered concentrated

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Pd(OAc)2 (123.6 mg, 0.55 mmol), PPh3 (557.5 mg, 2.2 mmol), K2CO3 (3.8 g, 27.5 mmol) and 3-bromo-2-fluorobenzamide (4.0 g, 18.4 mmol) were suspended in 1,4-dioxane (30 mL). After the mixture was heated to 80° C. for 15 min, [3-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)phenyl]boronic acid (5.9 g, 22.0 mmol) was added. Then the reaction mixture was stirred over night at 100° C. After cooling to room temperature, the solvent was removed under reduced pressure. The residue was dissolved in CH2Cl2 (50 mL), then was washed with water (20 mL), brine (20 mL), and dried over Na2SO4. After the solvent was removed, the crude product was purified on an Al2O3 column chomatography, eluting with CH2Cl2/CH3OH (300:1). 3′-({[(1,1-Dimethylethyl)(dimethyl)silyl]oxy}methyl)-2-fluoro-3-biphenylcarboxamide, was obtained (4.1 g, yield: 63%). 1H NMR (400 MHz, CDCl3) δ 0.12 (s, 6H), 0.95 (s, 9H), 4.81 (s, 2H), 7.25-8.12 (m, 7H). After cooling to room temperature the solvent was removed under reduced pressure The residue was dissolved in CH2Cl2 (50 mL) was washed with water (20 mL), brine (20 mL) dried over Na2SO4 After the solvent was removed the crude product was purified on an Al2O3 column chomatography eluting with CH2Cl2/CH3OH (300:1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-bromo-2-fluorobenzamide (3.0 g, 13.76 mmol) in THF (50 mL) was added BH3.Me2S (1.57 mL, 20.6 mmol) and the mixture was stirred at 50° C. for 2 h (monitored by TLC). The reaction was quenched by adding HCl (20 mL, 3 N) after which the result mixture was stirred for 2 h and then THF was removed under vacuum. The aqueous layer was extracted with AcOEt (30 mL), and then was adjusted to pH=9.0 with NaOH (1 N). Then the aqueous layer was extracted with AcOEt (50 mL×2). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated to give 1.30 g of the title compound as a colorless oil (yield: 46%). 1H NMR (400 MHz, D2O) δ 4.30 (S, 2H), 7.19-7.22 (m, 1H), 7.47 (t, J=8.8 Hz, 1 H), 7.73-7.77 (m, 1H); 13C NMR (100 MHz, D2O) δ 37.4, 108.9, 121.2, 126.2, 130.7, 135.1, 156.2, 158.6. The reaction was quenched by adding HCl (20 mL, 3 N) after which the result mixture THF was removed under vacuum The aqueous layer was extracted with AcOEt (30 mL) Then the aqueous layer was extracted with AcOEt (50 mL×2) The combined organic layers were washed with brine dried over Na2SO4 filtered concentrated

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Pd(OAc)2 (123.6 mg, 0.55 mmol), PPh3 (557.5 mg, 2.2 mmol), K2CO3 (3.8 g, 27.5 mmol) and 3-bromo-2-fluorobenzamide (4.0 g, 18.4 mmol) were suspended in 1,4-dioxane (30 mL). After the mixture was heated to 80° C. for 15 min, [3-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)phenyl]boronic acid (5.9 g, 22.0 mmol) was added. Then the reaction mixture was stirred over night at 100° C. After cooled to room temperature, the solvent was removed under reduced pressure. The residue was dissolved in CH2Cl2 (50 mL), then was washed with water (20 mL), brine (20 mL), and dried over Na2SO4. After the solvent was removed, the crude product was purified on Al2O3 column chromatography, eluting with CH2Cl2/CH3OH (300:1). 4.1 g of the product, 3′-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)-2-fluoro-3-biphenylcarboxamide, was obtained (yield: 63%). 1H NMR (400 MHz, CDCl3): δ 0.12 (s, 6 H), 0.95 (s, 9 H), 4.81 (s, 2 H), 7.25-8.12 (m, 7 H). After cooled to room temperature the solvent was removed under reduced pressure The residue was dissolved in CH2Cl2 (50 mL) was washed with water (20 mL), brine (20 mL) dried over Na2SO4 After the solvent was removed the crude product was purified on Al2O3 column chromatography eluting with CH2Cl2/CH3OH (300:1)

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Pd(OAc)2 (123.6 mg, 0.55 mmol), PPh3 (557.5 mg, 2.2 mmol), K2CO3 (3.8 g, 27.5 mmol) and 3-bromo-2-fluorobenzamide (4.0 g, 18.4 mmol) were suspended in 1,4-dioxane (30 mL). After the mixture was heated to 80° C. for 15 min, [3-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)phenyl]boronic acid (5.9 g, 22.0 mmol) was added. Then the reaction mixture was stirred over night at 100° C. After cooled to room temperature, the solvent was removed under reduced pressure. The residue was dissolved in CH2Cl2 (50 mL), then was washed with water (20 mL), brine (20 mL), and dried over Na2SO4. After the solvent was removed, the crude product was purified on Al2O3 column chromatography, eluting with CH2Cl2/CH3OH (300:1). 4.1 g of the product, 3′-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)-2-fluoro-3-biphenylcarboxamide, was obtained (yield: 63%). 1H NMR (400 MHz, CDCl3): δ 0.12 (s, 6 H), 0.95 (s, 9 H), 4.81 (s, 2 H), 7.25-8.12 (m, 7 H). After cooled to room temperature the solvent was removed under reduced pressure The residue was dissolved in CH2Cl2 (50 mL) was washed with water (20 mL), brine (20 mL) dried over Na2SO4 After the solvent was removed the crude product was purified on Al2O3 column chromatography eluting with CH2Cl2/CH3OH (300:1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-bromo-2-fluorobenzamide (3.0 g, 13.76 mmol) in THF (50 mL) was added BH3.Me2S (1.57 mL, 20.6 mmol) and stirred at 50° C. for 2 h (monitored by TLC). The reaction was quenched by adding HCl (20 mL, 3 N) and the result mixture was stirred for 2 h before THF was removed under vacuum. The aqueous layer was extracted with AcOEt (30 mL), and then was adjusted to pH=9.0 with NaOH (1 N). The aqueous layer was extracted with AcOEt (50 mL×2). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated to give 1.30 g of the title compound, as a colorless oil (yield: 46%). 1H NMR (400 MHz, D2O): δ 4.30 (S, 2 H), 7.19-7.22 (m, 1 H), 7.47 (t, J=8.8 Hz, 1 H), 7.73-7.77 (m, 1 H); 13C NMR (100 MHz, D2O): δ 37.4, 108.9, 121.2, 126.2, 130.7, 135.1, 156.2, 158.6. The reaction was quenched by adding HCl (20 mL, 3 N) was removed under vacuum The aqueous layer was extracted with AcOEt (30 mL) The aqueous layer was extracted with AcOEt (50 mL×2) The combined organic layers were washed with brine dried over Na2SO4 filtered concentrated

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-bromo-2-fluorobenzoic acid (3.77 g, 17.2 mmol) in dry tetrahydrofuran (200 ml) was added triethylamine (4.77 ml, 34.4 mmol) and thionyl chloride (1.69 ml, 21.5 mmol). The reaction mixture was stirred for 1 h and then quenched with ammonia in methanol (10 ml, saturated). After an additional hour of stirring the mixture was evaporated and the crude product was purified by flash column chromatography (ethyl acetate/isooctane 1:1) to give the title compound (1.76 g). MS m/z (rel. intensity, 70 eV) 219 (M+, 26), 217 (M+, 26), 203 (62), 201 (70), 94 (bp). quenched with ammonia in methanol (10 ml, saturated) After an additional hour of stirring the mixture was evaporated the crude product was purified by flash column chromatography (ethyl acetate/isooctane 1:1)