With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.56-54-2,(S)-(6-methoxyquinolin-4-yl)((1S,2R,4S,5R)-5-vinylquinuclidin-2-yl)methanol,as a common compound, the synthetic route is as follows.,56-54-2
General procedure: (Part 1) To a stirred solution of Cinchona alkaloid (either Quinine, Quinidine, Cinchonine or Cinchonidine) (1 equiv.) in THF (0.1 M) was added the required arylmethyl halide compound (1.2 equiv.) at room temperature. The reaction mixture was refluxed overnight, cooled to room temperature and all volatiles were removed invacuo. The residue was then dissolved in CH2Cl2 (typically 2 mL for 1 mmol of starting material) and the resulting solution was added dropwise onto Et2O (typically 30 mL for 1 mmol of starting material) with vigorous stirring. The resulting precipitate was then filtered, washed thoroughly with Et2O, and further dried under high vacuum for 2 hours, yielding the intermediate alcohol product in an excellent yield. (Part2) This product (1 equiv.) was dissolved in CH2Cl2 (0.2 M). Methyl iodide (3 equiv.) and an aqueous sodium hydroxide solution (50 %w, 5 equiv.) were successively added at room temperature. The reaction mixturewas stirred at room temperature for 4 h, before water (typically 20 mL for 1 mmol of starting material) was added to quench the reaction. The organic layer was separated and the aqueous layer was extracted with CH2Cl2. The combined organic extracts were dried over Na2SO4, and concentrated in vacuo (N.B: washing with brine is prohibited to avoid the I/Cl anion exchange). Purification by column chromatography on silica gel, eluting with MeOH/Acetone/CH2Cl2 (0:10:90 to 10:10:90), afforded the desired Cinchona alkaloid quaternary ammonium salt in a moderate to excellent yield.
The synthetic route of 56-54-2 has been constantly updated, and we look forward to future research findings.
Reference£º
Article; Antien, Kevin; Viault, Guillaume; Pouysegu, Laurent; Peixoto, Philippe A.; Quideau, Stephane; Tetrahedron; vol. 73; 26; (2017); p. 3684 – 3690;,
Metal catalyst and ligand design
Ligand Template Strategies for Catalyst Encapsulation – NCBI