Method for preparing apalutamide intermediate as drug for treating prostate cancer through catalysis

[0043] Preparation of hydrotalcite-supported Ni / Ce composite metal oxides:

[0044] (A) Preparation of Ni / Ce composite metal oxide:

[0045] (A-1) 10mmol Ce(NO 3 ) 3 ·6H 2 O and 40mmol Ni(NO 3 ) 2 ·6H 2 Add O into 500ml of water, heat up to 40-45°C and use a paddle stirrer to stir and dissolve to obtain a metal salt mixture;

[0046] (A-2) Add the alkaline mixed solution dropwise to the metal salt mixed solution to maintain the pH between 10.5-11.0 to generate solid particles; after the pH is stable, heat up to 60-70°C and keep stirring for 2-3 days; the alkali The mixed solution is a mixed aqueous solution of sodium hydroxide of 0.5mol / L and sodium carbonate of 0.3mol / L;

[0047] (A-3) After cooling to room temperature, filter, wash the filter cake with deionized water, and then vacuum-dry at 70-80°C to constant weight to obtain a composite metal oxide precursor;

[0048] (A-4) Calcining the composite metal oxide precursor at a high temperature of 400-450° C. in

[0064] Using Cat / 200 in Example 1 as the catalyst, the amount of catalyst, the type of hydrogen donor, and the solvent were further optimized, and the optimization process was as follows:

[0065] Substrate 2-cyano-3-trifluoromethyl-5-nitropyridine (10mmol, 2.17g), catalyst Cat / 200 (0.05-0.4 times the substrate weight), 20ml solvent and hydrogen donor 60mmol at 50 Magnetic stirring reaction at -60°C, the reaction solution was taken every 1h for HPLC detection, and the reaction effect of the statistical system (reaction time, conversion rate of substrate 2-cyano-3-trifluoromethyl-5-nitropyridine and The selectivity of its target product), see shown in table 2:

[0066] Table 2 Optimization of nitro reduction reaction

[0067]

[0068]

[0069] Note: a, the amount of Cat / 200 means that the amount of Cat / 200 added is a multiple of the amount of substrate added; the low selectivity in b is due to the transition state of some nitro groups reduced to amino groups, such a

[0072] After the reaction system was determined, the catalytic system was scaled up at the level of 100 grams, and the steps were as follows:

[0073] S1: Add 2.5L of isopropanol to a 5L double-layer glass reactor with a paddle stirrer, and add 2-cyano-3-trifluoromethyl-5-nitropyridine (217g, 1mol) under nitrogen protection , catalyst Cat / 200 (43.4g, 20%wt);

[0074] S2: Turn on the stirring and control the rotation speed to 200rpm, then raise the temperature to 50-60°C at a heating rate of 2°C / min, and when the temperature reaches 55°C, the heat preservation timer will react;

[0075] S3: After the timing reaction for 2 hours, take the reaction solution and carry out HPLC detection (result: the conversion rate is 89.2%, and the selectivity is 92.3%), continue the insulation reaction for 1 hour, and take the reaction solution for HPLC detection (the conversion rate is 99.8%, and the selectivity is 96.3%) );

[0076] S4: naturally cool down to room temperature, and then filt