| 65 - 74% |
With sodium hydroxide; sodium hypochlorite; In water; ethyl acetate; at -5℃; for 1 - 1.5h;Product distribution / selectivity; |
A glass reactor equipped with a stirrer is charged with ethyl acetate (3286 mL) and 5- 5 (difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl]thio]-lH-benzimidazole ("thioether") (260,0 g) is added. The flask is cooled to -5 0C, and mixture of 275,6 mL aqueous 16,9% active sodium hypochlorite solution (or corresponding quantity depending on active chlorine assay) and 10% sodium hydroxide solution (291,2 g) is dropped in approximately 1 hour. Oxidation reaction is monitored by IR spectroscopy 0 method as described above. After the aimed chemical conversion is achieved by the addition of extra oxidant defined through extrapolation, as described above, the reaction is stopped by interrupting the addition of further amounts of sodium hypochlorite. After stirring for a 5 minutes, aqueous 10% Na2S2O3 (614 g) is added dropwise over 15 minutes, additionally stirred for 15 minutes, the phases are then separated. The organic 5 layer is washed twice with 15% sodium carbonate solution (1390 mL). To the organic layer activated charcoal (13 g) is added and after stirring for 15 minutes mixture is filtrated. Organic layer is concentrated to give residue (600 mL) and after cooling to the room temperature acetone (858 mL) is added. By cooling the solution to 5C and stirring it for 2 hours at this temperature crystallization occurs. A precipitate is filtered 0 off to give pantoprazole sodium salt monohydrate. <n="18"/>5-(Difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)metliyl]sulfinyl]-lH- benzimidazole sodium salt monohydrate (Pantoprazole Sodium Salt Monohydrate)The above results show that the reaction conditions can be varied to a large degree but using the process of the invention high quality pantoprazole is produced with low amounts of sulfone (III) present; Into a reactor with impeller agitator is charged ethyl acetate (13,9 L) and after that 5- (difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl]thio]-lH-benzimidazole ("thioether") (1,1 kg) is added. The reactor is cooled to-5 C, and mixture of 3,75 kg aqueous 15,2% active sodium hypochlorite solution (or corresponding quantity depending on active chlorine assay) and 10% sodium hydroxide solution (2,91 kg) is dropped for 90 minutes. The oxidation reaction is monitored by IR spectroscopy method. After the chemical conversion is achieved, reaction is stopped by stopping of the addition of further amounts of sodium hypochlorite. After stirring for a 15 minutes, aqueous 10% Na2S2O3 (2,6 kg) is added drop wise with aim of the decomposition of any possible unreacted sodium hypochlorite. The content of reactor is stirred for an additional 15 minutes and the aqueous layer is separated from organic layer. The organic layer is washed twice with 15% sodium carbonate solution (11,7 L). To the organic layer activated charcoal (60 g) in ethyl acetate (0,5 L) is added and after stirring for 15 minutes mixture is filtrated. Organic layer is concentrated to give residue (2,5 L) and after cooling to the room temperature acetone (3,6 L) is added. By cooling the solution to 5C and stirring it for 2,5 hours at this temperature crystallization occurs. A precipitate is filtered off to give pantoprazole sodium salt monohydrate. |
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
