136918-14-4

1469-48-3

The general procedure for the synthesis of tetrahydrophenamine from 3-hydroxy-1H-isoindol-1-one was as follows: 30 g (0.20 mol) of phthalimide, 600 ml of N,N-dimethylformamide (DMF), and 9 g of nickel Nguyenne were added to a 1L stainless steel magnetically stirred autoclave, and the reactor was sealed. After displacing the air in the kettle under nitrogen protection, stirring was started and the temperature was gradually increased. When the temperature rose to 110°C, the gauge pressure showed 0 MPa. At this time, hydrogen was introduced into the kettle to keep the reaction temperature between 105 and 115°C. The reaction was carried out under the protection of nitrogen. After 70 minutes of reaction, the pressure gauge was observed to rise, at which time the hydrogen inlet valve was closed and stirring was continued for 30 minutes until the pressure gauge returned to zero. Repeat the process of passing and stopping hydrogen as described above, making sure to stop the flow of hydrogen each time the pressure gauge indicated pressure, and then pass hydrogen again when the pressure returned to zero. After the total reaction time reached 10 hours, the reaction mixture was cooled to 40°C, the gas in the kettle was replaced with nitrogen and the reaction solution was poured out. The reaction solution was filtered to remove the catalyst and the filtrate was transferred to a rotary evaporator. DMF was removed by distillation under reduced pressure using a water-circulating vacuum pump, and the distillation was stopped after collecting about 550 ml of distillate. Cooling to room temperature precipitated a large number of white granular crystals, which were filtered through a Büchner funnel and the filtrate was combined with the distillate. The filter cake was washed with 20 ml of water and dried to give 30 g of pure white crystalline powder. The product had a melting point of 134.5°C~135.4°C. The purity was 99.51% by liquid chromatography, and the yield of phthalimide was 97.40%.