Method for preparing esomeprazole
A technology for esomeprazole and compounds, applied in the field of synthesis of esomeprazole, capable of solving problems such as poor process reproducibility, low utilization rate of raw materials by split method, increased production cost, etc.
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Embodiment 1
[0028] The impact of embodiment 1 bidentate ligand structure on esomeprazole synthesis
[0029] A mixed solvent of 20ml of NMP and dichloromethane (V:V=1:4) dissolves 4g of Ufeprazole (1 equivalent), the temperature of the solution is lowered to 0°C, and 0.5 equivalent of N-substituted (1R,2S)-1- Amino-2-indanol and 0.25 equivalent of tetraisopropyl titanate, then dropwise add 1 equivalent of cumene hydroperoxide in NMP and dichloromethane mixed solvent solution 7ml, after 20 minutes, the temperature is raised to 25°C. After reacting for 6h-10h, 5ml of ammonia water (10%) solution was added to terminate the reaction, and samples were taken for HPLC detection (results are shown in Table 1). Take the sample number 3 in the table below to continue processing, add acetic acid aqueous solution (5%) to adjust pH=8-9, separate layers, extract the aqueous phase with dichloromethane (8ml*3) 3 times, and combine the organic phases. Na 2 SO 4 Dry, filter, concentrate, and recrystalliz...
Embodiment 2
[0032] The influence of embodiment 2 reaction solvents on esomeprazole synthesis
[0033] Take 5ml of NMP mixed with dichloromethane in different proportions and dissolve 1g of Ufeprazole (1 equivalent) in a mixed solvent, the temperature of the solution is lowered to 0°C, and 0.5 equivalent of N-benzyl-(1R,2S)-1-amino-2 - indanol and 0.25 equivalent of tetraisopropyl titanate, then dropwise add 1 equivalent of cumene hydroperoxide in NMP and dichloromethane mixed solvent solution 2ml, dropwise in 5 minutes, raise the temperature to 25 ° C for 6 hours, add 2ml10% ammonia solution to stop the reaction, sampling HPLC detection, the results are shown in the table below
[0034] The influence of table 2 ligand structure on esomeprazole synthesis
[0035] serial number
Embodiment 3
[0036] Embodiment 3 adopts the influence of different oxidizing agents on esomeprazole synthesis
[0037]Take 5ml of NMP and dichloromethane (V: V = 1: 4) mixed solvent to dissolve 1 g of Ufeprazole (1 equivalent), the temperature of the solution is lowered to 0 ° C, and 0.5 equivalent of N-benzyl-(1R, 2S)- 1-Amino-2-indanol and 0.25 equivalent of tetraisopropyl titanate, then dropwise add 1 equivalent of hydrogen peroxide derivative in NMP and dichloromethane mixed solvent solution 2ml, dropwise for 5 minutes, heat up to 35°C React for 6h-10h, add 2ml of 10% ammonia solution to terminate the reaction, take a sample for HPLC detection, the results are shown in the table below
[0038] The oxidant used in table 3 is on the influence of esomeprazole synthesis
[0039] serial number
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