5-bromo-2-(2-ethylpiperidin-1-yl)benzaldehyde

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

Procedure: To a solution of 5-bromo-2-(2-ethylpiperidin-1-yl)benzaldehyde (obtained in step 1, 10 g, 0.0484 mol) in methanol (100 mL) under nitrogen, was added sodium borohydride (1.28 g, 0.0484 mol) at 0° C. in portions. After being stirred at room temperature for a period of 1 h, the reaction mixture was evaporated to remove methanol. The resulting crude product was taken in water (100 mL) and extracted in ethyl acetate. The separated organic layer was washed with water, dried over sodium sulphate and concentrated under reduced pressure to afford the titled compound as yellow liquid (8.8 g, 88%). 1H NMR (DMSO-d6, 400 MHz) δ 7.54-7.55 (1H, s), 7.34-7.54 (1H, m), 7.07-7.09 (1H, d), 5.17-5.20 (1H, t), 4.59-4.64 (1H, d), 4.43-4.48 (1H, d), 2.77-2.84 (2H, m), 2.442-2.449 (1H, m), 1.74 (2H, t), 1.53-1.56 (2H, t), 1.32-1.34 (2H, m), 1.15-1.19 (2H, m), 0.60-0.64 (3H, t). the reaction mixture was evaporated to remove methanol extracted in ethyl acetate The separated organic layer was washed with water dried over sodium sulphate concentrated under reduced pressure

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-bromo-2-fluorobenzaldehyde (20 g, 0.099 mol) in dimethyl sulfoxide (230 mL) and water (70 mL), were added 2-ethylpiperidine (14.4 mL, 0.1083 mol) and sodium carbonate (20.88 g, 0.197 mol). The resulting mixture was heated at 110° C. for a period of 30 h. The reaction mixture was cooled to room temperature, diluted with water (1000 mL), extracted by methyl tert-butyl ether (2×500 mL), dried using sodium sulphate and concentrated under reduced pressure. The resulting crude was purified by column chromatography on silica gel (60-120 mesh) using pet ether as eluent to afford the titled compound as a yellow liquid. 1H NMR (DMSO-d6, 400 MHz) δ 10.15 (1H, s), 7.70-7.73 (2H, d), 7.22-7.25 (1H, m), 3.08-3.13 (2H, m), 2.84-2.86 (1H, m), 1.83-1.84 (1H, m), 1.34-1.67 (7H, m), 0.62-0.66 (3H, t). The reaction mixture was cooled to room temperature extracted by methyl tert-butyl ether (2×500 mL) dried concentrated under reduced pressure The resulting crude was purified by column chromatography on silica gel (60-120 mesh)

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

Procedure: To a solution of 5-bromo-2-(2-ethylpiperidin-1-yl)benzaldehyde (obtained in step 1, 10 g, 0.0484 mol) in methanol (100 mL) under nitrogen, was added sodium borohydride (1.28 g, 0.0484 mol) at 0° C. in portions. After being stirred at room temperature for a period of 1 h, the reaction mixture was evaporated to remove methanol. The resulting crude product was taken in water (100 mL) and extracted in ethyl acetate. The separated organic layer was washed with water, dried over sodium sulphate and concentrated under reduced pressure to afford the titled compound as yellow liquid (8.8 g, 88%). 1H NMR (DMSO-d6, 400 MHz) δ 7.54-7.55 (1H, s), 7.34-7.54 (1H, m), 7.07-7.09 (1H, d), 5.17-5.20 (1H, t), 4.59-4.64 (1H, d), 4.43-4.48 (1H, d), 2.77-2.84 (2H, m), 2.442-2.449 (1H, m), 1.74 (2H, t), 1.53-1.56 (2H, t), 1.32-1.34 (2H, m), 1.15-1.19 (2H, m), 0.60-0.64 (3H, t). the reaction mixture was evaporated to remove methanol extracted in ethyl acetate The separated organic layer was washed with water dried over sodium sulphate concentrated under reduced pressure

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-bromo-2-fluorobenzaldehyde (20 g, 0.099 mol) in dimethyl sulfoxide (230 mL) and water (70 mL), were added 2-ethylpiperidine (14.4 mL, 0.1083 mol) and sodium carbonate (20.88 g, 0.197 mol). The resulting mixture was heated at 110° C. for a period of 30 h. The reaction mixture was cooled to room temperature, diluted with water (1000 mL), extracted by methyl tert-butyl ether (2×500 mL), dried using sodium sulphate and concentrated under reduced pressure. The resulting crude was purified by column chromatography on silica gel (60-120 mesh) using pet ether as eluent to afford the titled compound as a yellow liquid. 1H NMR (DMSO-d6, 400 MHz) δ 10.15 (1H, s), 7.70-7.73 (2H, d), 7.22-7.25 (1H, m), 3.08-3.13 (2H, m), 2.84-2.86 (1H, m), 1.83-1.84 (1H, m), 1.34-1.67 (7H, m), 0.62-0.66 (3H, t). The reaction mixture was cooled to room temperature extracted by methyl tert-butyl ether (2×500 mL) dried concentrated under reduced pressure The resulting crude was purified by column chromatography on silica gel (60-120 mesh)

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-bromo-2-fluorobenzaldehyde (20 g, 0.099 mol) in dimethyl sulfoxide (230 mL) and water (70 mL), were added 2-ethylpiperidine (14.4 mL, 0.1083 mol) and sodium carbonate (20.88 g, 0.197 mol). The resulting mixture was heated at 110° C. for a period of 30 h. The reaction mixture was cooled to room temperature, diluted with water (1000 mL), extracted by methyl tert-butyl ether (2×500 mL), dried using sodium sulphate and concentrated under reduced pressure. The resulting crude was purified by column chromatography on silica gel (60-120 mesh) using pet ether as eluent to afford the titled compound as a yellow liquid. 1H NMR (DMSO-d6, 400 MHz) δ 10.15 (1H, s), 7.70-7.73 (2H, d), 7.22-7.25 (1H, m), 3.08-3.13 (2H, m), 2.84-2.86 (1H, m), 1.83-1.84 (1H, m), 1.34-1.67 (7H, m), 0.62-0.66 (3H, t). The reaction mixture was cooled to room temperature extracted by methyl tert-butyl ether (2×500 mL) dried concentrated under reduced pressure The resulting crude was purified by column chromatography on silica gel (60-120 mesh)

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

Procedure: To a solution of 5-bromo-2-(2-ethylpiperidin-1-yl)benzaldehyde (10 g, 48.4 mmol) in methanol (100 mL) under nitrogen was added sodium borohydride (1.28 g, 48.4 mmol) at 0° C. in portions. The reaction mixture was stirred at RT for 1 hour, then evaporated to remove methanol. The resulting crude was taken up with water (100 mL) and extracted with EtOAc. The organic layer was washed with water, then dried (Na2SO4) and concentrated under reduced pressure to afford the title compound as a yellow oil (8.8 g, 88%). 1H NMR (DMSO-d6, 400 MHz) δ 7.55 (1H, s), 7.34-7.54 (1H, m), 7.08 (1H, d), 5.19 (1H, t), 4.62 (1H, d), 4.46 (1H, d), 2.77-2.84 (2H, m), 2.45 (1H, m), 1.74 (2H, t), 1.55 (2H, t), 1.33 (2H, m), 1.17 (2H, m), 0.62 (3H, t). evaporated to remove methanol extracted with EtOAc The organic layer was washed with water dried (Na2SO4) concentrated under reduced pressure

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-bromo-2-fluorobenzaldehyde (20 g, 99 mmol) in DMSO (230 mL) and water (70 mL) were added 2-ethylpiperidine (14.4 mL, 108 mmol) and sodium carbonate (20.9 g, 197 mmol). The resulting mixture was heated at 110° C. for 30 hours. The reaction mixture was cooled at RT, diluted with water (1000 mL) and extracted with MTBE (2×500 mL). The organic layers were combined, dried (Na2SO4) and concentrated under reduced pressure. After purification by flash chromatography (silica, pet ether), the title compound was obtained as a yellow oil. 1H NMR (DMSO-d6, 400 MHz) δ 10.15 (1H, s), 7.72 (2H, d), 7.24 (1H, m), 3.11 (2H, m), 2.85 (1H, m), 1.84 (1H, m), 1.34-1.67 (7H, m), 0.64 (3H, t). The reaction mixture was cooled at RT extracted with MTBE (2×500 mL) dried (Na2SO4) concentrated under reduced pressure After purification by flash chromatography (silica, pet ether)

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-bromo-2-fluorobenzaldehyde (20 g, 99 mmol) in DMSO (230 mL) and water (70 mL) were added 2-ethylpiperidine (14.4 mL, 108 mmol) and sodium carbonate (20.9 g, 197 mmol). The resulting mixture was heated at 110° C. for 30 hours. The reaction mixture was cooled at RT, diluted with water (1000 mL) and extracted with MTBE (2×500 mL). The organic layers were combined, dried (Na2SO4) and concentrated under reduced pressure. After purification by flash chromatography (silica, pet ether), the title compound was obtained as a yellow oil. 1H NMR (DMSO-d6, 400 MHz) δ 10.15 (1H, s), 7.72 (2H, d), 7.24 (1H, m), 3.11 (2H, m), 2.85 (1H, m), 1.84 (1H, m), 1.34-1.67 (7H, m), 0.64 (3H, t). The reaction mixture was cooled at RT extracted with MTBE (2×500 mL) dried (Na2SO4) concentrated under reduced pressure After purification by flash chromatography (silica, pet ether)

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

Procedure: To a solution of 5-bromo-2-(2-ethylpiperidin-1-yl)benzaldehyde (10 g, 48.4 mmol) in methanol (100 mL) under nitrogen was added sodium borohydride (1.28 g, 48.4 mmol) at 0° C. in portions. The reaction mixture was stirred at RT for 1 hour, then evaporated to remove methanol. The resulting crude was taken up with water (100 mL) and extracted with EtOAc. The organic layer was washed with water, then dried (Na2SO4) and concentrated under reduced pressure to afford the title compound as a yellow oil (8.8 g, 88%). 1H NMR (DMSO-d6, 400 MHz) δ 7.55 (1H, s), 7.34-7.54 (1H, m), 7.08 (1H, d), 5.19 (1H, t), 4.62 (1H, d), 4.46 (1H, d), 2.77-2.84 (2H, m), 2.45 (1H, m), 1.74 (2H, t), 1.55 (2H, t), 1.33 (2H, m), 1.17 (2H, m), 0.62 (3H, t). evaporated to remove methanol extracted with EtOAc The organic layer was washed with water dried (Na2SO4) concentrated under reduced pressure

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-bromo-2-fluorobenzaldehyde (20 g, 99 mmol) in DMSO (230 mL) and water (70 mL) were added 2-ethylpiperidine (14.4 mL, 108 mmol) and sodium carbonate (20.9 g, 197 mmol). The resulting mixture was heated at 110° C. for 30 hours. The reaction mixture was cooled at RT, diluted with water (1000 mL) and extracted with MTBE (2×500 mL). The organic layers were combined, dried (Na2SO4) and concentrated under reduced pressure. After purification by flash chromatography (silica, pet ether), the title compound was obtained as a yellow oil. 1H NMR (DMSO-d6, 400 MHz) δ 10.15 (1H, s), 7.72 (2H, d), 7.24 (1H, m), 3.11 (2H, m), 2.85 (1H, m), 1.84 (1H, m), 1.34-1.67 (7H, m), 0.64 (3H, t). The reaction mixture was cooled at RT extracted with MTBE (2×500 mL) dried (Na2SO4) concentrated under reduced pressure After purification by flash chromatography (silica, pet ether)

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

Procedure: To a solution of 5-bromo-2-(2-ethylpiperidin-1-yl)benzaldehyde (obtained in step 1, 10 g, 0.0484 mol) in methanol (100 mL) under nitrogen, was added sodium borohydride (1.28 g, 0.0484 mol) at 0° C. in portions. After being stirred at room temperature for a period of 1 h, the reaction mixture was evaporated to remove methanol. The resulting crude product was taken in water (100 mL) and extracted in ethyl acetate. The separated organic layer was washed with water, dried over sodium sulphate and concentrated under reduced pressure to afford the titled compound as yellow liquid (8.8 g, 88%). 1H NMR (DMSO-d6, 400 MHz) δ 7.54-7.55 (1H, s), 7.34-7.54 (1H, m), 7.07-7.09 (1H, d), 5.17-5.20 (1H, t), 4.59-4.64 (1H, d), 4.43-4.48 (1H, d), 2.77-2.84 (2H, m), 2.442-2.449 (1H, m), 1.74 (2H, t), 1.53-1.56 (2H, t), 1.32-1.34 (2H, m), 1.15-1.19 (2H, m), 0.60-0.64 (3H, t). the reaction mixture was evaporated to remove methanol extracted in ethyl acetate The separated organic layer was washed with water dried over sodium sulphate concentrated under reduced pressure

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-bromo-2-fluorobenzaldehyde (20 g, 0.099 mol) in dimethyl sulfoxide (230 mL) and water (70 mL), were added 2-ethylpiperidine (14.4 mL, 0.1083 mol) and sodium carbonate (20.88 g, 0.197 mol). The resulting mixture was heated at 110° C. for a period of 30 h. The reaction mixture was cooled to room temperature, diluted with water (1000 mL), extracted by methyl tert-butyl ether (2×500 mL), dried using sodium sulphate and concentrated under reduced pressure. The resulting crude was purified by column chromatography on silica gel (60-120 mesh) using pet ether as eluent to afford the titled compound as a yellow liquid. 1H NMR (DMSO-d6, 400 MHz) δ 10.15 (1H, s), 7.70-7.73 (2H, d), 7.22-7.25 (1H, m), 3.08-3.13 (2H, m), 2.84-2.86 (1H, m), 1.83-1.84 (1H, m), 1.34-1.67 (7H, m), 0.62-0.66 (3H, t). The reaction mixture was cooled to room temperature extracted by methyl tert-butyl ether (2×500 mL) dried concentrated under reduced pressure The resulting crude was purified by column chromatography on silica gel (60-120 mesh)