Candesartan cilexetil synthesis

7synthesis methods

Product Name:Candesartan cilexetil
CAS Number:145040-37-5
Molecular formula:C33H34N6O6
Molecular Weight:610.66

170791-09-0
221 suppliers
$12.00/1g

145040-37-5
639 suppliers
$6.00/10mg

Yield:145040-37-5 98%

Reaction Conditions:

with hydrogenchloride in methanol;dichloromethane at -14 - -12;Flow reactor;Large scale;Temperature;

Steps:

1.III

III.Distilled methylene chloride (58.8 kg) into the reaction vessel, added triphenyl candesartan cilexetil (10.0 kg, 11.72 mol) prepared in Step II, and 75 kg of methanol that was frozen in advance to turn cold salt on. The temperature was lowered to reduce the temperature of the kettle. -14°C;Add 7% HCl methanol (34.5 kg, HCl 66.16 mol) frozen in advance to the kettle, keep the kettle temperature at -12°C-13°C, react for 3 hours, and monitor with TLC (dichloromethane:methanol=20:1). After completion of the reaction, 6% aqueous ammonia was added to adjust the pH of the organic layer to 5.5, 290 kg of water was further added, and the mixture was stirred for 10 minutes. The mixture was allowed to stand for separation, and the separated organic layer was dried over anhydrous sodium sulfate. The desiccant was removed by filtration, and the filtrate was recovered under reduced pressure at 35[deg.] C. to obtain a viscous product.Anhydrous ethyl ether (45kg) was added to the viscous material in the kettle and stirred at 12°C for 20 minutes. A large amount of solids appeared, the stirring was stopped, the temperature was lowered to 0°C, and the mixture was allowed to stand for 3 hours. The filter cake was filtered and the cake was dried at normal pressure for 12 hours. Crude candesartan ester 7.0 kg was obtained. Calculated according to the following formula, the yield of this step is 98%.

References:

CN105153124,2018,B Location in patent:Paragraph 0006; 0068; 0084; 0098

78-09-1 Synthesis