Preparation method of 2-aminopyridine-4-methyl alcohol intermediate

[0021] Example 1

[0022] A preparation method of intermediate 2-aminopyridine-4-methanol includes the following steps:

[0023] (1) Add ZnCl to 4-methylpyridine-2-carboxaldehyde 2 , Control the temperature to 80℃, and pass in chlorine gas under light conditions, and the chlorine gas flow rate is 0.3L / min. After full reaction, stop the passage of chlorine gas and filter to remove ZnCl 2 , Prepare 4-chloromethylpyridine-2-carboxaldehyde, add it to toluene and mix well, adjust the temperature to 60℃, add MnCl 2 , Under stirring conditions, add H dropwise to it 2 O 2 After reacting for 1 hour, stop the reaction, and after filtering, prepare a mixture containing 4-chloromethylpyridine-2-carboxylic acid;

[0024] (2) Reduce the prepared mixture containing 4-chloromethylpyridine-2-carboxylic acid to a temperature of 0°C, add triethylamine and mix well, then add DPPA and stir for 45 minutes, then heat for reflux reaction for 6 hours, and make it through fractional distillation 2-amino-4-chlo

[0028] Example 2

[0029] A preparation method of intermediate 2-aminopyridine-4-methanol includes the following steps:

[0030] (1) Add ZnCl to 4-methylpyridine-2-carboxaldehyde 2 , Control the temperature to 90°C, pass in chlorine gas under light conditions, and the chlorine flow rate is 0.3L / min. After full reaction, stop passing in chlorine gas, and filter to remove ZnCl 2 , Prepare 4-chloromethylpyridine-2-carboxaldehyde, add it to toluene and mix well, adjust the temperature to 75℃, add MnCl 2 , Under stirring conditions, add H dropwise to it 2 O 2 After reacting for 2h, stop the reaction, and after filtering, prepare a mixture containing 4-chloromethylpyridine-2-carboxylic acid;

[0031] (2) Reduce the prepared mixture containing 4-chloromethylpyridine-2-carboxylic acid to a temperature of 4°C, add triethylamine and mix well, then add DPPA and stir for 90 minutes, then heat to reflux for 6-9 hours. After fractional distillation Prepare 2-amino-4-chloromethylpyridine;

[0032] (3

[0035] Example 3

[0036] A preparation method of intermediate 2-aminopyridine-4-methanol includes the following steps:

[0037] (1) Add ZnCl to 4-methylpyridine-2-carboxaldehyde 2 , Control the temperature to 80℃, and pass in chlorine gas under light conditions, and the chlorine gas flow rate is 0.3L / min. After full reaction, stop the passage of chlorine gas and filter to remove ZnCl 2 , Prepare 4-chloromethylpyridine-2-carboxaldehyde, add it to toluene and mix well, adjust the temperature to 75℃, add MnCl 2 , Under stirring conditions, add H dropwise to it 2 O 2 After reacting for 1 hour, stop the reaction, and after filtering, prepare a mixture containing 4-chloromethylpyridine-2-carboxylic acid;

[0038] (2) Lower the prepared mixture containing 4-chloromethylpyridine-2-carboxylic acid to a temperature of 4°C, add triethylamine and mix well, then add DPPA and stir for 45 minutes, then heat for reflux reaction for 9 hours, and make it through fractional distillation 2-amino-4-chlor