24-norursodeoxycholic acid synthesis

Yield: 98%

Reaction Conditions:

with perlite in water;isopropyl alcohol at 0 - 80; for 4 h;Product distribution / selectivity;

Steps:

4.a
Product III, 2-propanol and one equivalent of potassium hydroxide are mixed and heated to 70 to 80°C. Water is slowly added until a solution is obtained. The solution is light yellow to yellow and slightly turbid. Active carbon and perlite are added and the solution is filtered while hot. Under reduced pressure 2-propanol/water are distilled off at 40 to 80°C. By addition of 2-propanolol, the distillation is continued until the water content is < 2%. Thereafter, the suspension is cooled to 5 to 15°C (>4 hours). The temperature is lowered to 0 to 5°C and product IV is filtered off, washed with 2-propanol and dried under reduced pressure <50°C. Product IV is obtained as a white solid. In case the obtained potassium salt is not of sufficient purity it can be re-crystalised:Product IV and 2-propanol are mixed and heated to 75 to 80°C. Water is added until a solution is obtained. 2-Propanol/water are distilled off under reduced pressure at 40 to 80°C. During the distillation product IV starts crystallizing. Again, the distillation is continued until the water content is < 2%. 2-Propanol is added and the suspension is cooled to 5 to 15°C (>4 hours). The temperature is lowered to 0 to 5°C and product V is filtered off, washed with 2- propanol and dried under reduced pressure <50°C. The re-crystallization is repeated until the test for purity is compliant (product V is obtained pharmaceutical pure and at very high yields of > 98%, a proof of very efficient purification).

References:

DR. FALK PHARMA GMBH;WILHELM, Rudolf;PRÖLS, Markus;FISCHER, Erik;WAENERLUND POULSEN, Heidi WO2012/72689, 2012, A1 Location in patent:Page/Page column 17-18