methyl 2-amino-3-methoxybenzoate

反応条件: temp:0.00; pressure:0.00; stir:

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 methyl 2-amino-3-methoxybenzoate (13.0 g, 71.8 mmol) in DMF (30 mL) was added NBS (14.38 g, 80.8 mmol) at room temperature and the resulting reaction mixture was stirred for 17 h. The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by column chromatography (silica gel, 2% to 5% EtOAc in hexanes) to afford methyl 2-amino-5-bromo-3-methoxybenzoate (13.7 g, 73%). 1H NMR consistent. the resulting reaction mixture The reaction mixture was filtered through Celite the filtrate was concentrated under reduced pressure The resulting residue was purified by column chromatography (silica gel, 2% to 5% EtOAc in hexanes)

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

実験手順: To a solution of methyl 2-amino-3-methoxybenzoate (13.0 g, 71.8 mmol) in DMF (30 mL) was added NBS (14.38 g, 80.8 mmol) at room temperature and the resulting reaction mixture was stirred for 17 h. The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by column chromatography (silica gel, 2% to 5% EtOAc in hexanes) to afford methyl 2-amino-5-bromo-3-methoxybenzoate (13.7 g, 73%). 1H NMR consistent. the resulting reaction mixture The reaction mixture was filtered through Celite the filtrate was concentrated under reduced pressure The resulting residue was purified by column chromatography (silica gel, 2% to 5% EtOAc in hexanes)

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

実験手順: A suspension of methyl-2-amino-3-methoxybenzoate (Intermediate 36, 2.27 g, 12.5 mmol) in water (10 mL) and con. HCl (2 mL) was cooled to 0 deg. C. and a solution of sodium nitrite (1.04 g, 15 mmol) in water (10 mL) was added dropwise. The resulting solution was stirred cold for 30 min. then added to a suspension of copper(I)cyanide (3.4 g, 38 mmol) in water (100 mL). The resulting suspension was heated at 60 deg. C. for 3 h, cooled, chloroform was added and the mixture was filtered through celite. The organic layer was dried (MgSO4), the solvent was evaporated and the residue was flash chromatographed eluting with 0-50% hexane-ethyl acetate affording Intermediate 37 (0.56 g, 23.5%) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ ppm 3.99 (s, 6 H), 7.20 (d, J=8.35 Hz, 1 H), 7.61 (t, J=8.13 Hz, 1 H), 7.68 (d, J=7.47 Hz, 1 H). The resulting suspension was heated at 60 deg. C for 3 h cooled the mixture was filtered through celite The organic layer was dried (MgSO4) the solvent was evaporated chromatographed eluting with 0-50% hexane-ethyl acetate affording Intermediate 37 (0.56 g, 23.5%) as a yellow solid

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

実験手順: To a solution of compound 53 (22.4 g, 123 mmol) in DMF (250 mL) was added N-bromosuccinimide (21.9 g, 123 mmol) portionwise at 0° C. The mixture was stirred at 0° C. for 0.5 h. To the mixture was added water and extracted with EtOAc (500 mL×2). The combined organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography to provide the desired compound 54 (27.5 g, 86%) as a white solid. extracted with EtOAc (500 mL×2) The combined organic layer was dried over MgSO4 filtered concentrated in vacuo The residue was purified by silica gel column chromatography

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

実験手順: To a solution of compound 53 (22.4 g, 123 mmol) in DMF (250 mL) was added N-bromosuccinimide (21.9 g, 123 mmol) portionwise at 0° C. The mixture was stirred at 0° C. for 0.5 h. To the mixture was added water and extracted with EtOAc (500 mL×2). The combined organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography to provide the desired compound 54 (27.5 g, 86%) as a white solid. extracted with EtOAc (500 mL×2) The combined organic layer was dried over MgSO4 filtered concentrated in vacuo The residue was purified by silica gel column chromatography

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

実験手順: A suspension of compound 52 (26.2 g, 124 mmol) and Pd/C (10 wt. %, 6.0 g) in THF (400 mL) and MeOH (200 mL) was stirred under an atmosphere of H2 at room temperature for 18 hours. EtOAc (300 mL) was added to the mixture and filtered through a Celite pad. The filtrate was concentrated in vacuo to provide the crude product 53 (22.4 g, 99%) as colorless oil. filtered through a Celite pad The filtrate was concentrated in vacuo

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

実験手順: One hundred thirty-three grams (0.63 mol) of methyl 3-methoxy-2-nitro-benzoate are dissolved in 1000 ml of toluene and hydrogenated in an autoclave at ambient temperature and under a hydrogen pressure of 5 bar in the presence of platinum over a period of two hours. The catalyst is removed by filtration, the residue is dried with sodium sulfate, and the toluene is distilled off in vacuo. Oil, RF value: 0.8 [silica gel plate; chloroform/acetone (9:1)], hydrogenated in an autoclave at ambient temperature and under a hydrogen of two hours The catalyst is removed by filtration the residue is dried with sodium sulfate the toluene is distilled off in vacuo

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

実験手順: One hundred thirty-three grams (0.63 mol) of methyl 3-methoxy-2-nitro-benzoate are dissolved in 1000 ml of toluene and hydrogenated in an autoclave at ambient temperature and under a hydrogen pressure of 5 bar in the presence of platinum over a period of two hours. The catalyst is removed by filtration, the residue is dried with sodium sulfate, and the toluene is distilled off in vacuo. Oil, RF value: 0.8 [silica gel plate; chloroform/acetone (9:1)], hydrogenated in an autoclave at ambient temperature and under a hydrogen of two hours The catalyst is removed by filtration the residue is dried with sodium sulfate the toluene is distilled off in vacuo

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

実験手順: To a solution of methyl 2-amino-3-methoxybenzoate (13.0 g, 71.8 mmol) in DMF (30 mL) was added NBS (14.38 g, 80.8 mmol) at room temperature and the resulting reaction mixture was stirred for 17 h. The reaction mixture was filtered through Celite, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by column chromatography (silica gel, 2% to 5% EtOAc in hexanes) to afford methyl 2-amino-5-bromo-3-methoxybenzoate (13.7 g, 73%). 1H NMR consistent. the resulting reaction mixture The reaction mixture was filtered through Celite the filtrate was concentrated under reduced pressure The resulting residue was purified by column chromatography (silica gel, 2% to 5% EtOAc in hexanes)

反応条件: temp:0.00; pressure:0.00; stir: