ethyl 7-fluoro-1-benzofuran-2-carboxylate

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of ethyl 7-fluorobenzofuran-2-carboxylate (3.70 g, 17.8 mmol) in tetrahydrofuran (70 mL) was added lithium aluminum hydride (6.7 mL, 2.0 M solution in tetrahydrofuran, 13.3 mmol) at 0° C. The mixture was stirred at 0° C. for 0.5 h and solid sodium sulfate decahydrate (15.0 g) was added slowly in portions. The mixture was stirred at 0° C. for 10 min and at ambient temperature for 30 min. The solid was filtered off and washed with ethyl acetate (3×150 mL). The combined filtrate was washed with brine (150 mL), dried over anhydrous magnesium sulfate, filtered, concentrated in vacuo. The residue was purified by column chromatography (hexanes/ethyl acetate, 7/1→4/1) to afford (7-fluorobenzofuran-2-yl)methanol (2.4 g, 81%) as a colorless solid: 1H NMR (300 MHz, CDCl3) δ7.34-7.29 (m, 1H), 7.19-7.10 (m, 1H), 7.06-6.98 (m, 1H), 6.73-6.69 (m, 1H), 4.82-4.78 (m, 2H), 2.07-2.01 (m, 1H); MS (ES+) m/z 167.1 (M+1). The mixture was stirred at 0° C. for 10 min and at ambient temperature for 30 min The solid was filtered off washed with ethyl acetate (3×150 mL) The combined filtrate was washed with brine (150 mL) dried over anhydrous magnesium sulfate filtered concentrated in vacuo The residue was purified by column chromatography (hexanes/ethyl acetate, 7/1→4/1)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of ethyl 7-fluorobenzofuran-2-carboxylate (3.70 g, 17.8 mmol) in tetrahydrofuran (70 mL) was added lithium aluminum hydride (6.7 mL, 2.0 M solution in tetrahydrofuran, 13.3 mmol) at 0° C. The mixture was stirred at 0° C. for 0.5 h and solid sodium sulfate decahydrate (15.0 g) was added slowly in portions. The mixture was stirred at 0° C. for 10 min and at ambient temperature for 30 min. The solid was filtered off and washed with ethyl acetate (3×150 mL). The combined filtrate was washed with brine (150 mL), dried over anhydrous magnesium sulfate, filtered, concentrated in vacuo. The residue was purified by column chromatography (hexanes/ethyl acetate, 7/1→4/1) to afford (7-fluorobenzofuran-2-yl)methanol (2.4 g, 81%) as a colorless solid: 1H NMR (300 MHz, CDCl3) δ7.34-7.29 (m, 1H), 7.19-7.10 (m, 1H), 7.06-6.98 (m, 1H), 6.73-6.69 (m, 1H), 4.82-4.78 (m, 2H), 2.07-2.01 (m, 1H); MS (ES+) m/z 167.1 (M+1). The mixture was stirred at 0° C. for 10 min and at ambient temperature for 30 min The solid was filtered off washed with ethyl acetate (3×150 mL) The combined filtrate was washed with brine (150 mL) dried over anhydrous magnesium sulfate filtered concentrated in vacuo The residue was purified by column chromatography (hexanes/ethyl acetate, 7/1→4/1)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of ethyl 7-fluorobenzofuran-2-carboxylate (3.70 g, 17.8 mmol) in tetrahydrofuran (70 mL) was added lithium aluminum hydride (6.7 mL, 2.0 M solution in tetrahydrofuran, 13.3 mmol) at 0° C. The mixture was stirred at 0° C. for 0.5 h and solid sodium sulfate decahydrate (15.0 g) was added slowly in portions. The mixture was stirred at 0° C. for 10 min and at ambient temperature for 30 min. The solid was filtered off and washed with ethyl acetate (3×150 mL). The combined filtrate was washed with brine (150 mL), dried over anhydrous magnesium sulfate, filtered, concentrated in vacuo. The residue was purified by column chromatography (hexanes/ethyl acetate, 7/1→4/1) to afford (7-fluorobenzofuran-2-yl)methanol (2.4 g, 81%) as a colorless solid: 1H NMR (300 MHz, CDCl3) δ7.34-7.29 (m, 1H), 7.19-7.10 (m, 1H), 7.06-6.98 (m, 1H), 6.73-6.69 (m, 1H), 4.82-4.78 (m, 2H), 2.07-2.01 (m, 1H); MS (ES+) m/z 167.1 (M+1). The mixture was stirred at 0° C. for 10 min and at ambient temperature for 30 min The solid was filtered off washed with ethyl acetate (3×150 mL) The combined filtrate was washed with brine (150 mL) dried over anhydrous magnesium sulfate filtered concentrated in vacuo The residue was purified by column chromatography (hexanes/ethyl acetate, 7/1→4/1)

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

Procedure: A mixture of 3-fluoro-2-hydroxybenzaldehyde (5.00 g, 35.7 mmol), potassium carbonate (9.85 g, 71.4 mmol), and ethyl bromoacetate (4.30 ml, 39.3 mmol) in N,N-dimethylformamide (70 mL) was heated at 100° C. for 16 h. The mixture was diluted with water (500 mL) and extracted with ethyl acetate (3×150 mL). The combined organic solution was washed with brine (150 mL), dried over anhydrous magnesium sulfate, filtered, concentrated in vacuo. The residue was purified by column chromatography (hexanes/ethyl acetate, 49/1→9/1) to afford ethyl 7-fluorobenzofuran-2-carboxylate (3.86 g, 52%) as a yellowish oil: 1H NMR (300 MHz, CDCl3) δ7.56-7.54 (m, 1H), 7.47-7.42 (m, 1H), 7.28-7.14 (m, 2H), 4.46 (q, J=7.1 Hz, 2H), 1.43 (t, J=7.1 Hz, 3H). extracted with ethyl acetate (3×150 mL) The combined organic solution was washed with brine (150 mL) dried over anhydrous magnesium sulfate filtered concentrated in vacuo The residue was purified by column chromatography (hexanes/ethyl acetate, 49/1→9/1)

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

Procedure: A mixture of 3-fluoro-2-hydroxybenzaldehyde (5.00 g, 35.7 mmol), potassium carbonate (9.85 g, 71.4 mmol), and ethyl bromoacetate (4.30 ml, 39.3 mmol) in N,N-dimethylformamide (70 mL) was heated at 100° C. for 16 h. The mixture was diluted with water (500 mL) and extracted with ethyl acetate (3×150 mL). The combined organic solution was washed with brine (150 mL), dried over anhydrous magnesium sulfate, filtered, concentrated in vacuo. The residue was purified by column chromatography (hexanes/ethyl acetate, 49/1→9/1) to afford ethyl 7-fluorobenzofuran-2-carboxylate (3.86 g, 52%) as a yellowish oil: 1H NMR (300 MHz, CDCl3) δ7.56-7.54 (m, 1H), 7.47-7.42 (m, 1H), 7.28-7.14 (m, 2H), 4.46 (q, J=7.1 Hz, 2H), 1.43 (t, J=7.1 Hz, 3H). extracted with ethyl acetate (3×150 mL) The combined organic solution was washed with brine (150 mL) dried over anhydrous magnesium sulfate filtered concentrated in vacuo The residue was purified by column chromatography (hexanes/ethyl acetate, 49/1→9/1)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of ethyl 7-fluorobenzofuran-2-carboxylate (3.70 g, 17.8 mmol) in tetrahydrofuran (70 mL) was added lithium aluminum hydride (6.7 mL, 2.0 M solution in tetrahydrofuran, 13.3 mmol) at 0° C. The mixture was stirred at 0° C. for 0.5 h and solid sodium sulfate decahydrate (15.0 g) was added slowly in portions. The mixture was stirred at 0° C. for 10 min and at ambient temperature for 30 min. The solid was filtered off and washed with ethyl acetate (3×150 mL). The combined filtrate was washed with brine (150 mL), dried over anhydrous magnesium sulfate, filtered, concentrated in vacuo. The residue was purified by column chromatography (hexanes/ethyl acetate, 7/1-4/1) to afford (7-fluorobenzofuran-2-yl)methanol (2.4 g, 81%) as a colorless solid: 1H NMR (300 MHz, CDCl3) δ7.34-7.29 (m, 1H), 7.19-7.10 (m, 1H), 7.06-6.98 (m, 1H), 6.73-6.69 (m, 1H), 4.82-4.78 (m, 2H), 2.07-2.01 (m, 1H); MS (ES+) m/z 167.1 (M+1). The mixture was stirred at 0° C. for 10 min and at ambient temperature for 30 min The solid was filtered off washed with ethyl acetate (3×150 mL) The combined filtrate was washed with brine (150 mL) dried over anhydrous magnesium sulfate filtered concentrated in vacuo The residue was purified by column chromatography (hexanes/ethyl acetate, 7/1-4/1)

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

Procedure: A mixture of 3-fluoro-2-hydroxybenzaldehyde (5.00 g, 35.7 mmol), potassium carbonate (9.85 g, 71.4 mmol), and ethyl bromoacetate (4.30 ml, 39.3 mmol) in N,N-dimethylformamide (70 mL) was heated at 100° C. for 16 h. The mixture was diluted with water (500 mL) and extracted with ethyl acetate (3×150 mL). The combined organic solution was washed with brine (150 mL), dried over anhydrous magnesium sulfate, filtered, concentrated in vacuo. The residue was purified by column chromatography (hexanes/ethyl acetate, 49/1→9/1) to afford ethyl 7-fluorobenzofuran-2-carboxylate (3.86 g, 52%) as a yellowish oil: 1H NMR (300 MHz, CDCl3) δ7.56-7.54 (m, 1H), 7.47-7.42 (m, 1H), 7.28-7.14 (m, 2H), 4.46 (q, J=7.1 Hz, 2H), 1.43 (t, J=7.1 Hz, 3H). extracted with ethyl acetate (3×150 mL) The combined organic solution was washed with brine (150 mL) dried over anhydrous magnesium sulfate filtered concentrated in vacuo The residue was purified by column chromatography (hexanes/ethyl acetate, 49/1→9/1)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of ethyl 7-fluorobenzofuran-2-carboxylate (3.70 g, 17.8 mmol) in tetrahydrofuran (70 mL) was added lithium aluminum hydride (6.7 mL, 2.0 M solution in tetrahydrofuran, 13.3 mmol) at 0° C. The mixture was stirred at 0° C. for 0.5 h and solid sodium sulfate decahydrate (15.0 g) was added slowly in portions. The mixture was stirred at 0° C. for 10 min and at ambient temperature for 30 min. The solid was filtered off and washed with ethyl acetate (3×150 mL). The combined filtrate was washed with brine (150 mL), dried over anhydrous magnesium sulfate, filtered, concentrated in vacuo. The residue was purified by column chromatography (hexanes/ethyl acetate, 7/1→4/1) to afford (7-fluorobenzofuran-2-yl)methanol (2.4 g, 81%) as a colorless solid: 1H NMR (300 MHz, CDCl3) δ7.34-7.29 (m, 1H), 7.19-7.10 (m, 1H), 7.06-6.98 (m, 1H), 6.73-6.69 (m, 1H), 4.82-4.78 (m, 2H), 2.07-2.01 (m, 1H); MS (ES+) m/z 167.1 (M+1). The mixture was stirred at 0° C. for 10 min and at ambient temperature for 30 min The solid was filtered off washed with ethyl acetate (3×150 mL) The combined filtrate was washed with brine (150 mL) dried over anhydrous magnesium sulfate filtered concentrated in vacuo The residue was purified by column chromatography (hexanes/ethyl acetate, 7/1→4/1)

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

Procedure: A mixture of 3-fluoro-2-hydroxybenzaldehyde (5.00 g, 35.7 mmol), potassium carbonate (9.85 g, 71.4 mmol), and ethyl bromoacetate (4.30 ml, 39.3 mmol) in N,N-dimethylformamide (70 mL) was heated at 100° C. for 16 h. The mixture was diluted with water (500 mL) and extracted with ethyl acetate (3×150 mL). The combined organic solution was washed with brine (150 mL), dried over anhydrous magnesium sulfate, filtered, concentrated in vacuo. The residue was purified by column chromatography (hexanes/ethyl acetate, 49/1→9/1) to afford ethyl 7-fluorobenzofuran-2-carboxylate (3.86 g, 52%) as a yellowish oil: 1H NMR (300 MHz, CDCl3) δ7.56-7.54 (m, 1H), 7.47-7.42 (m, 1H), 7.28-7.14 (m, 2H), 4.46 (q, J=7.1 Hz, 2H), 1.43 (t, J=7.1 Hz, 3H). extracted with ethyl acetate (3×150 mL) The combined organic solution was washed with brine (150 mL) dried over anhydrous magnesium sulfate filtered concentrated in vacuo The residue was purified by column chromatography (hexanes/ethyl acetate, 49/1→9/1)