methyl 5-bromo-2-ethylbenzoate

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Add N-bromosuccinimide (1090 g, 6.12 mol) and 2,2′-azo-bis-isobutyronitrile (11.4 g, 0.069 mol) to a 20° C. solution of methyl 5-bromo-2-ethylbenzoate (1296 g, 5.33 mol) in carbon tetrachloride (7 L). Heat to reflux for 4 hours, cool to 20-30° C. and wash with water (10 L), extract the aqueous phase with dichloromethane (5 L), combine the organic layers, and wash with water (10 L), Na2SO3 (5 L) and saturated aqueous sodium chloride. Dry with sodium sulfate, filter, and evaporate under reduced pressure to give the title compound as a pale yellow solid (1791 g, 104% crude). ES/MS m/z: 241 (M−HBr). Heat to reflux for 4 hours wash with water (10 L) extract the aqueous phase with dichloromethane (5 L) wash with water (10 L), Na2SO3 (5 L) and saturated aqueous sodium chloride Dry with sodium sulfate filter evaporate under reduced pressure

反応条件: temp:62.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Add diethyl zinc (3050 mL, 3.05 mol, 1 M hexane) over 3 hours to a 5° C. solution of methyl 5-bromo-2-iodobenzoate (1876 g, 5.50 mol) and (1,1′-bis(diphenylphosphino)ferrocene)palladium(II) chloride (40 g, 0.05 mol). Heat the mixture to 60-65° C. over 2 hours and stir for an additional 2 hours, then cool to 10-15° C. and pour into ice cold aqueous 1 M HCl (10 L). Separate the phases, extract the aqueous layer with methyl-tert-butyl ether (2×10 L), combine the organic phases, wash with saturated aqueous sodium chloride, dry over sodium sulfate, filter, and evaporate under reduced pressure. Dissolve in ethyl acetate (400 mL) and add petroleum ether (8 L), then let stand at 15-20° C. for 16 hours and filter through a pad of silica gel, wash with ethyl acetate/petroleum ether (1:20, 8 L) and evaporate the filtrate under reduced pressure to provide the title compound as a pale yellow oil (1306 g, 96%). ES/MS m/e: (79Br/81Br) 243/245 (M+H). cool to 10-15° C. Separate the phases extract the aqueous layer with methyl-tert-butyl ether (2×10 L) wash with saturated aqueous sodium chloride dry over sodium sulfate filter evaporate under reduced pressure Dissolve in ethyl acetate (400 mL) add petroleum ether (8 L) let stand at 15-20° C. for 16 hours filter through a pad of silica gel wash with ethyl acetate/petroleum ether (1:20, 8 L) evaporate the filtrate under reduced pressure

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

実験手順: The above methyl 2-ethylbenzoate was mixed with molecular sieve 13× (powder, 70 g), and while stirring the mixture, bromine (5.2 ml) was added dropwise thereto at 80° C. The mixture was further stirred at the same temperature for 1.5 hours. The mixture was cooled to room temperature, and added thereto were potassium carbonate (7.4 g), water (70 ml) and methanol (350 ml), and the mixture was stirred for 8 hours. Insoluble materials were filtered off, and suspended in a mixed solution of methanol (500 ml)-water (500 ml), and the mixture was stirred at room temperature overnight. Insoluble materials were filtered off and the filtrate was combined with the previously obtained filtrate, and the solvent was evaporated under reduced pressure. The residue was extracted with ethyl acetate, and the extract was washed with brine, and dried over sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was distilled under reduced pressure, to give methyl 5-bromo-2-ethylbenzoate (2.44 g). APCI-Mass m/Z 260/262 (M+NH4). was added dropwise at 80° C added the mixture was stirred for 8 hours Insoluble materials were filtered off the mixture was stirred at room temperature overnight Insoluble materials were filtered off the solvent was evaporated under reduced pressure The residue was extracted with ethyl acetate the extract was washed with brine dried over sodium sulfate The solvent was evaporated under reduced pressure the residue was distilled under reduced pressure