Application of 112734-22-2, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 112734-22-2 name is (4-Bromo-2-fluorophenyl)methanamine, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.
Example 12 Preparation of (3R)-2′-(4-bromo-2-fluorobenzyl)spiro[pyrrolidin-3,4′(1’H)-pyrrolo[1,2-a]pyrazin]-1′,2,3′,5(2’H)-tetraone 2,5-Dimethoxytetrahydrofuran (7.4 g) and 2.5% aqueous acetic acid (50 g) were added to ethyl (2R)-2-amino-2-ethoxycarbonylsuccinimide (10 g)and the mixture was stirred at 70C for 1.5 hours. The reaction solution was cooled and insoluble materials were dissolved by addition of ethyl acetate (50 ml) and stirring. The mixture was placed for a while and the organic layer was separated from the aqueous layer, washed with brine, dried over magnesium sulfate and filtered. The filtrate was concentrated in vacuo, diisopropylether (37 g) and ethyl acetate (9.2 g) were added to the residue and diisopropylamine (6.2 g) was added and the mixture was stirred at 0-5C of inner temperature. The precipitated crystals were filtered, washed with diisopropylether and dried to give (2R)-2-ethoxycarbonyl-2-(pyrrol-1-yl)succinimide diisopropylamine salt(yield 88%). To a suspension of (2R)-2-ethoxycarbonyl-2-(pyrrol-1-yl)succinimide diisopropylamine salt (20.0 g) in ethyl acetate (100 ml), was added 20% aqueous sulfuric acid (16 ml) and the salt was dissolved. The solution was placed after stirring and the organic layer was separated with the aqueous layer. The organic layer was separated with the aqueous layer again after brine was added to the organic solution, and the mixture was stirred and placed. The organic layer was concentrated in vacuo, ethyl acetate (50 ml) and trichloroacetyl chloride (32.3 g) were added to the residue and the mixture was stirred under reflux for 6 hours. The reaction solution was cooled, ethyl acetate (134 ml) was added thereto and it was washed with brine, aqueous solution of sodium bicarbonate, 5% aqueous sulfuric acid and brine successively. The organic layer was concentrated in vacuo, N-methyl pyrrolidone (26 ml) and ethyl acetate(6.7 ml) were added and the residue was dissolved. The solution was cooled and diisopropylamine (9 g) was added thereto and the mixture was stirred. 4-Bromo-2-fluorobenzylamine (24.2 g) was added dropwise under ice-cooling and the mixture was stirred at 0-5C for 18 hours. Ethyl acetate (266 ml) was added to the reaction solution and it was washed with 5% aqueous sulfuric acid, aqueous solution of sodium bicarbonate, 5% aqueous sulfuric acid and brine successively. The organic layer was concentrated in vacuo, ethanol (100 ml) was added to the residue and it was dissolved under heating to reflux. Ethanol (33 ml) was evaporated, the concentrated solution was cooled with ice-water and the precipitated crystals were filtered and washed with ethanol. The resulting wet crystals were recrystallized from isopropanol (124 ml and 180 ml) twice to give (3R)-2′-(4-bromo-2-fluorobenzyl)spiro[pyrrolidin-3,4′(1’H)-pyrrolo[1,2-a]pyrazin]-1′,2,3′,5(2’H)-tetraone (yield 58%).
At the same time, in my other blogs, there are other synthetic methods of this type of compound, (4-Bromo-2-fluorophenyl)methanamine, and friends who are interested can also refer to it.
Reference:
Patent; Dainippon Sumitomo Pharma Co., Ltd.; Katayama Seiyakusyo Co. Ltd.; EP2058300; (2009); A1;,
Bromide – Wikipedia,
bromide – Wiktionary