- Preparation method of salbutamol sulfate intermediate
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The invention provides a preparation method of a salbutamol sulfate intermediate. Salbutamol is a beta receptor stimulant; a current preparation technology of the salbutamol mainly takes an original research technology as a main part; the original research technology takes p-hydroxyacetophenone as a starting material and the salbutamol is prepared through chloromethylation, esterification, bromination, amination, hydrolysis and reduction. An existing synthesis method of the salbutamol sulfate intermediate is used for synthesizing through a plurality of steps and is complicated to operate; theloss of products in a preparation process is great and the technological time is relatively long. The preparation method of the salbutamol sulfate intermediate, provided by the invention, comprises the following steps: reducing carbonyl of a compound I under the action of a reducing agent to obtain a compound II; then adding a debenzylation reagent and carrying out debenzylation reaction to obtainthe salbutamol sulfate intermediate III. According to the preparation method, the salbutamol sulfate intermediate III is prepared from the compound I by adopting a 'one-pot method'; operation steps are reduced, the reaction time is shortened and the reaction yield is improved.
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Page/Page column 5-7
(2019/06/05)
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- A Combined High-Throughput Screening and Reaction Profiling Approach toward Development of a Tandem Catalytic Hydrogenation for the Synthesis of Salbutamol
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A combined high-throughput screening and reaction profiling approach to the telescoping of two reductions in the synthesis of Salbutamol is described. Optimization studies revealed the beneficial effect of mildly acidic conditions, and the use of water as a cosolvent. Persistent formation of deoxygenated impurities using a Pd/C catalyst led to the initiation of reaction profiling studies, which revealed that the ketone intermediate formed after rapid debenzylation is the sole source of deoxygenated impurities, indicating that more rapid ketone hydrogenation should minimize this deoxygenation. A dual catalyst approach based on these insights has been developed, with both Pd/Pt and Ru/Pt catalyst systems as more selective than Pd-only systems. Based on reaction profiles that indicate the deoxygenation side reaction is first-order in the concentration of debenzylated ketone intermediate, Pt catalysts for rapid and selective ketone hydrogenation were paired with Pd and Ru catalysts known to perform selective debenzylation. Optimization of these dual catalyst processes led to conditions that were demonstrated on 20 g scale to prepare Salbutamol in 49% isolated yield after recrystallization.
- Leitch, David C.,Greene, Thomas F.,O'Keeffe, Roisin,Lovelace, Thomas C.,Powers, Jeremiah D.,Searle, Andrew D.
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supporting information
p. 1806 - 1814
(2017/11/24)
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- Synthesis, isolation and characterization of process-related impurities in salbutamol sulphate
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Three known and one unknown impurities in salbutamol sulphate bulk drug at level 0.1% (ranging from 0.05-0.1%) were detected by gradient reverse phase high performance liquid chromatography. These impurities were preliminarily identified by the mass number of the impurities. Different experiments were conducted and finally synthesized and characterized the known and unknown imputities. Copyright E-Journal of Chemistry 2004-2011.
- Sharma, Yogesh Kumar,Agarwal, Dau Dayal,Bhure, Sudesh,Mukharjee, Rajendra Nath,Sahu, Pramod Kumar,Bhardwaj, Santosh
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experimental part
p. 1720 - 1727
(2012/05/19)
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