methyl 4-bromo-3-fluorobenzoate

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:

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:

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of compound 4-bromo-3-fluoro-benzoic acid methyl ester (1 g, 4.29 mmol), hydrazine hydrate (2.2 mL, 42.9 mmol) and MeOH (20 mL) was heated at 70° C. for overnight. Concentrated, diluted with EtOAc (300 mL) and washed with water (100 mL). The organic layer was dried over Na2SO4, filtered and concentrated give the desired product 2AR (0.9 g, 90%). Concentrated diluted with EtOAc (300 mL) washed with water (100 mL) The organic layer was 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 4-bromo-3-fluoro-benzoic acid methyl ester (5.3 g, 22.9 mmol) in dry THF (60 mL) was added diisobutylaluminum hydride (30 mL) dropwise, This mixture was stirred overnight at room temperature until the starting material had been consumed, quenched with saturated aqueous potassium tartrate solution and extracted with ethyl acetate (3×50 mL). The combined organic layer was washed with brine, dried with Na2SO4, filtered, and evaporated to give white solid product (4.3 g, 92%). had been consumed quenched with saturated aqueous potassium tartrate solution extracted with ethyl acetate (3×50 mL) The combined organic layer was washed with brine dried with Na2SO4 filtered evaporated

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

実験手順: To a solution of 4-bromo-3-fluoro-benzoic acid (5.0 g, 22.9 mmol) in MeOH (60 mL) was added thionyl chloride (10 mL), This mixture was heated for about 5 h at 80 degrees Celsius until the starting material had been consumed, and then evaporated in vacuo to give white solid product (5.3 g, 100%). This mixture was heated for about 5 h at 80 degrees Celsius until the starting material had been consumed evaporated in vacuo

反応条件: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 1-methylpiperazine (980 μl, 8.80 mmol) in toluene (15 ml) was added tris(dibenzylidene acetone)dipalladium (201 mg, 0.22 mmol), BINAP (550 mg, 0.88 mmol), and cesium carbonate (4.30 g, 13.2 mmol). The mixture was stirred for 30 minutes before the addition of methyl 4-bromo-3-fluorobenzoate (2.05 g, 8.80 mmol), after which, the temperature was increased to 105° C. and stirred for an additional 18 h. The mixture was cooled and filtered through Celite, washed with ethyl acetate, and the resultant filtrate concentrated in vacuo to afford an orange oil. The residue was purified by column chromatography eluting with 5% methanol in dichloromethane. Pure fractions were concentrated to afford (1.80 g, 81%) of methyl 3-fluoro-4-(4-methylpiperazin-1-yl)benzoate as a colorless oil. 1H NMR (400 MHz, CD3OD): 7.78-7.73 (d, 1H), 7.64-7.59 (d, 1H), 7.09-7.03 (m, 1H), 3.86 (s, 3H), 3.26-3.20 (m, 4H), 2.65-2.59 (m, 4H), 2.35 (s, 3H). MS (EI) for C13H17FN2O2: 253 (MH+). The mixture was cooled filtered through Celite washed with ethyl acetate the resultant filtrate concentrated in vacuo to afford an orange oil The residue was purified by column chromatography eluting with 5% methanol in dichloromethane Pure fractions were concentrated

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

実験手順: To 4-bromo-3-fluorobenzoic acid (2.00 g, 9.13 mmol) in methanol (12 ml) was added sulfuric acid (500 μl) and heated to 80° C. for 18 h then cooled to room temperature and concentrated. The residue was diluted with saturated sodium bicarbonate and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and then concentrated to afford (2.07 g, 97%) of methyl 4-bromo-3-fluorobenzoate, which was used without further purification. 1H NMR (400 MHz, CD3OD): 7.80-7.73 (m, 3H), 3.91 (s, 3H). MS (EI) for C8H6BrFO2: 234 (MH+). then cooled to room temperature concentrated The residue was diluted with saturated sodium bicarbonate extracted with ethyl acetate The organic layer was dried over sodium sulfate filtered concentrated

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

実験手順: To 4-bromo-3-fluorobenzoic acid (2.00 g, 9.13 mmol) in methanol (12 ml) was added sulfuric acid (500 μl) and heated to 80° C. for 18 h then cooled to room temperature and concentrated. The residue was diluted with saturated sodium bicarbonate and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and then concentrated to afford (2.07 g, 97%) of methyl 4-bromo-3-fluorobenzoate, which was used without further purification. 1H NMR (400 MHz, CD3OD): 7.80-7.73 (m, 3H), 3.91 (s, 3H). MS (EI) for C8H6BrFO2: 234 (MH+). then cooled to room temperature concentrated The residue was diluted with saturated sodium bicarbonate extracted with ethyl acetate The organic layer was dried over sodium sulfate filtered concentrated