methyl 3-bromo-5-(bromomethyl)benzoate

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Methyl 3-bromo-5-(bromomethyl)benzoate (2.1 g, 6.81 mmol) and tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate (1.8 g, 6.2 mmol) were combined in dimethylformamide (21 mL) and cooled to 0° C. The reaction was treated with sodium hydride (298 mg, 12.4 mmol), stirred at 0° C. for 1 h, and at room temperature for 30 min. The reaction was cooled to 0° C. and treated lithium hydroxide monohydrate (0.54 g, 13.6 mmol). The solution was stirred at room temperature for 16 h and the solvents evaporated. The resultant residue was diluted with water (10 mL) and the pH adjusted to ca. 1 with 1 N hydrochloric acid. The resultant white suspension was stored at 4° C. overnight and the product was collected by filtration, washed with a small amount of water, and dried in vacuo for several hours to afford 2.4 g (70%) as a white powder. LC/MS: tR=3.33 min, 506.20 (MH)+. (Phenomenex C18 4.6×50 mm, 10% MeOH/90% H2O/0.1% TFA→90% MeOH/10% H2O/0.1% TFA, Gradient time=4 min., Flow rate=4 mL/min.). at room temperature for 30 min The reaction was cooled to 0° C. The solution was stirred at room temperature for 16 h the solvents evaporated The resultant residue was diluted with water (10 mL) The resultant white suspension was stored at 4° C. overnight the product was collected by filtration washed with a small amount of water dried in vacuo for several hours to afford 2.4 g (70%) as a white powder

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Methyl 3-bromo-5-(hydroxymethyl)benzoate (2.0 g, 8.2 mmol) and triphenylphosphine (4.28 g, 16.3 mmol) were combined in tetrahydrofuran (20 mL) and cooled to 0° C. N-Bromosuccinimide (3.05 g, 17.1 mmol) was introduced in portions and the reaction allowed to warm to room temperature. After 16 h, the reaction mixture was diluted with ethyl acetate, washed with concentrated sodium bicarbonate (2×), then brine (2×), dried over sodium sulfate, and concentrated. Column chromatography on silica gel (10% ethylacete/hexanes) gave 2.1 g (83%) as a light brown oil. 1H-NMR (CDCl3, 300 MHz) δ 8.07 (s, 1H), 7.96 (s, 1H), 7.70 (s, 1H), 4.42 (s, 2H), 3.90 (s, 3H). Mass spec.: 308.93 (MH)+. to warm to room temperature washed with concentrated sodium bicarbonate (2×) brine (2×), dried over sodium sulfate concentrated Column chromatography on silica gel (10% ethylacete/hexanes) gave 2.1 g (83%) as a light brown oil

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Methyl 3-bromo-5-(bromomethyl)benzoate (2.1 g, 6.81 mmol) and tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate (1.8 g, 6.2 mmol) were combined in dimethylformamide (21 mL) and cooled to 0° C. The reaction was treated with sodium hydride (298 mg, 12.4 mmol), stirred at 0° C. for 1 h, and at room temperature for 30 min. The reaction was cooled to 0° C. and treated lithium hydroxide monohydrate (0.54 g, 13.6 mmol). The solution was stirred at room temperature for 16 h and the solvents evaporated. The resultant residue was diluted with water (10 mL) and the pH adjusted to ca. 1 with 1 N hydrochloric acid. The resultant white suspension was stored at 4° C. overnight and the product was collected by filtration, washed with a small amount of water, and dried in vacuo for several hours to afford 2.4 g (70%) as a white powder. LC/MS: tR=3.33 min, 506.20 (MH)+. (Phenomenex C18 4.6×50 mm, 10% MeOH/90% H2O/0.1% TFA→90% MeOH/10% H2O/0.1% TFA, Gradient time=4 min., Flow rate=4 mL/min.). at room temperature for 30 min The reaction was cooled to 0° C. The solution was stirred at room temperature for 16 h the solvents evaporated The resultant residue was diluted with water (10 mL) The resultant white suspension was stored at 4° C. overnight the product was collected by filtration washed with a small amount of water dried in vacuo for several hours to afford 2.4 g (70%) as a white powder

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Methyl 3-bromo-5-(hydroxymethyl)benzoate (2.0 g, 8.2 mmol) and triphenylphosphine (4.28 g, 16.3 mmol) were combined in tetrahydrofuran (20 mL) and cooled to 0° C. N-Bromosuccinimide (3.05 g, 17.1 mmol) was introduced in portions and the reaction allowed to warm to room temperature. After 16 h, the reaction mixture was diluted with ethyl acetate, washed with concentrated sodium bicarbonate (2×), then brine (2×), dried over sodium sulfate, and concentrated. Column chromatography on silica gel (10% ethylacete/hexanes) gave 2.1 g (83%) as a light brown oil. 1H-NMR (CDCl3, 300 MHz) δ 8.07 (s, 1H), 7.96 (s, 1H), 7.70 (s, 1H), 4.42 (s, 2H), 3.90 (s, 3H). Mass spec.: 308.93 (MH)+. to warm to room temperature washed with concentrated sodium bicarbonate (2×) brine (2×), dried over sodium sulfate concentrated Column chromatography on silica gel (10% ethylacete/hexanes) gave 2.1 g (83%) as a light brown oil

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Methyl 3-bromo-5-(bromomethyl)benzoate (2.1 g, 6.81 mmol) and tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate (1.8 g, 6.2 mmol) were combined in dimethylformamide (21 mL) and cooled to 0° C. The reaction was treated with sodium hydride (298 mg, 12.4 mmol), stirred at 0° C. for 1 h, and at room temperature for 30 min. The reaction was cooled to 0° C. and treated lithium hydroxide monohydrate (0.54 g, 13.6 mmol). The solution was stirred at room temperature for 16 h and the solvents evaporated. The resultant residue was diluted with water (10 mL) and the pH adjusted to ca. 1 with 1 N hydrochloric acid. The resultant white suspension was stored at 4° C. overnight and the product was collected by filtration, washed with a small amount of water, and dried in vacuo for several hours to afford 2.4 g (70%) as a white powder. LC/MS: tR=3.33 min, 506.20 (MH)+. (Phenomenex C18 4.6×50 mm, 10% MeOH/90% H2O/0.1% TFA→90% MeOH/10% H2O/0.1% TFA, Gradient time=4 min., Flow rate=4 mL/min.). at room temperature for 30 min The reaction was cooled to 0° C. The solution was stirred at room temperature for 16 h the solvents evaporated The resultant residue was diluted with water (10 mL) The resultant white suspension was stored at 4° C. overnight the product was collected by filtration washed with a small amount of water dried in vacuo for several hours to afford 2.4 g (70%) as a white powder

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Methyl 3-bromo-5-(hydroxymethyl)benzoate (2.0 g, 8.2 mmol) and triphenylphosphine (4.28 g, 16.3 mmol) were combined in tetrahydrofuran (20 mL) and cooled to 0° C. N-Bromosuccinimide (3.05 g, 17.1 mmol) was introduced in portions and the reaction allowed to warm to room temperature. After 16 h, the reaction mixture was diluted with ethyl acetate, washed with concentrated sodium bicarbonate (2×), then brine (2×), dried over sodium sulfate, and concentrated. Column chromatography on silica gel (10% ethylacete/hexanes) gave 2.1 g (83%) as a light brown oil. 1H-NMR (CDCl3, 300 MHz) δ 8.07 (s, 1H), 7.96 (s, 1H), 7.70 (s, 1H), 4.42 (s, 2H), 3.90 (s, 3H). Mass spec.: 308.93 (MH)+. to warm to room temperature washed with concentrated sodium bicarbonate (2×) brine (2×), dried over sodium sulfate concentrated Column chromatography on silica gel (10% ethylacete/hexanes) gave 2.1 g (83%) as a light brown oil