report one,
(1) Preparation of intermediate 2,6-dimethylaniline
24.43 g (0.2 mol) of 2,6-xylenol, 63.1 g (0.6 mol) of ammonia water, 1.06 g of 5% Pd/C, and 2.52 g (0.02 g of 2,6-dimethylcyclohexanone) were successively added to the reaction vessel. mol), reacted at 185 °C for 6 h, cooled to room temperature, filtered, recovered Pd/C and applied; the filtrate was distilled under reduced pressure, recovered 2,6-dimethylcyclohexanone and applied next time, the residue was washed with water once, and left to stand for stratification. , the oil layer is the intermediate 2,6-dimethylaniline 23.35g, the HPLC purity is 98.32%, and the yield is 94.73%.
(2) Preparation of Lidocain Hydrochlorid
To the there-necked flask with the distillation device, add 15.12g (0.28mol) of sodium methoxide, 24.24g (0.2mol) of the intermediate 2,6-dimethylaniline and 31.9g (0.22g) of N,N-diethylaminoacetate methyl ester successively. mol), heated to 95°C, and the methanol generated by the reaction was distilled off while reacting, until no methanol was evaporated, continued the reaction for 30 min, cooled to room temperature, added dichloroethane to dissolve, washed twice with water, and allowed to stand for stratification. The organic layer is the dichloroethane solution of lidocaine base.
In the dichloroethane solution of above-mentioned lidocaine base, add hydrochloric acid 2.56g, then adjust the pH to 3.5 with hydrogen chloride, add activated carbon to reflux for 20min, filter, concentrate the filtrate, crystallize by cooling, and dry to obtain Lidocain Hydrochlorid 48.28g, HPLC purity was 99.52%, the yield was 88.72%, and the total yield was 84.04%.
report two,
(1) Add acetone 200L, 2,6-dimethylaniline 50.0kg (412.6mol), potassium carbonate 142.6kg (1031.5mol) to the 500L enamel reaction kettle, stir and adjust the temperature of the material to 20±5°C, keep at Within this temperature range, 48.9 kg (433.2 mol) of chloroacetyl chloride was added dropwise at a high position, and the reaction was stirred at this temperature for 0.5 h after the dropping. Add 33.2kg (453.9mol) of diethylamine, heat to 60±5°C for 8h, filter, add hydrochloric acid to the filtrate with stirring, and adjust the pH of the filtrate to below 4.
(2) Concentrate the above reaction solution under reduced pressure at 50±5°C until no liquid is evaporated, add 200L acetone, heat and dissolve completely, add 2kg activated carbon, stir and decolorize at 55～65°C for 0.5h, press filter to clean area Crystallization kettle, stirring and cooling for crystallization, cooling to below -5°C for 3h, shaking off for filtration, and vacuum drying at 40-50°C in double cones for 4h to obtain 93.4kg of white crystalline powder, yield: 78.38%, HPLC normalized purity: 99.84 %.
