反应详情

温度

-78 °C

To a solution of 1-[3-bromo-5-(trifluoromethyl)phenyl]-N,N-dimethylmethanamine (2 g, 7.1 mmol) in THF (40 mL) at −78° C. was dropwise added a solution of n-butyllithium (2.50 M in hexane, 3.12 mL, 7.81 mmol). The resulting mixture was stirred at −78° C. for 20 min. Excess crushed solid CO2 was added and the mixture was stirred at −78° C. for another 15 min. The reaction was quenched by the addition of water (0.156 mL), and allowed to warm to room temperature. The solvents were evaporated and the solid was dried overnight under vacuum to give 3-[(dimethylamino)methyl]-5-(trifluoromethyl)benzoic acid.Li salt as a white solid contaminated with valeric acid. The crude acid was dissolved in aqueous hydrochloric acid (1M in water, 5 eq) and water (20 vols). Dissolution was not complete. The solids were removed by suction filtration, washed with methylene chloride and set aside. The resulting aqueous solution was transferred to a separatory funnel and washed with methylene chloride (3×). The washed aqueous phase was transferred to a round bottom flask. The filtered solids were added to the aqueous phase. The mixture was concentrated to dryness under reduced pressure. On heating in the water bath, the mixture turned homogeneous. On concentration, the solution afforded a gummy solid, which was azeotropically dried in toluene it was a free-flowing solid. The resulting powder was suspended in ether and filtered. The filter cake was briefly dried under suction. The product was transferred to a round bottom flask and dried under high vacuum at 40° C. overnight. LC-MS: (AA) ES+248; 1H NMR (400 MHz, CD3OD) δ ppm 8.46 (s, 1H), 8.39 (s, 1H), 8.14 (s, 1H), 4.51 (s, 2H), 2.89 (s, 6H).

1. additionwas added
2. stirringthe mixture was stirred at −78° C. for another 15 min
3. customThe reaction was quenched by the addition of water (0.156 mL)
4. temperatureto warm to room temperature
5. customThe solvents were evaporated
6. customthe solid was dried overnight under vacuum