Hydrochloric Acid → (R)-4-((3R,5S,6R,8S,9S,10S,13R,14S,17R)-6-ethyl-3-hydroxy-10,13-dimethyl-7-oxohexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoic acid

Temperature

100 °C

A mixture of purified compound 5 (110 g, 264 mmol), water (1100 mL), caustic soda solution (35.8 mL, 682 mmol) at 50% and palladium catalyst (Pd/C, 11 g) were charged to a hydrogenation reactor. The temperature was adjusted to 25° C. to 35° C. and the reactor was flushed three times with nitrogen (2 bar) and three times with hydrogen (1 bar). These pressure values were given relative to ambient pressure (=0 bar). A hydrogen pressure of 5 bar was applied and the reaction mixture was heated up to 100° C. (for isomerisation to the alpha position) over a period of 1.5 hours and then stirred for 3 hours while maintaining the hydrogen pressure at 4.5 to 5 bar. The reaction mixture is then cooled to 40° C. to 50° C. For the workup, the Pd/C is filtered off. To the filtrate, n-butyl acetate (1320 mL) and hydrochloric acid (67.8 mL, 815 mmol, 37%) were added. The aqueous phase was separated and discarded. The organic phase was treated with activated carbon (5.5 g) for about 10 minutes at 40 to 50° C. The activated carbon was filtered off and the filtrate was condensed by distillation and the resulting suspension was cooled to 15° C. to 20° C. within 2 to 3 hours. The precipitated compound 6 was isolated and washed with n-butyl acetate (160 mL). The product was filtered using a pressure filter. Drying was done in the pressure filter under vacuum at approximately 60° C. This leads to 89.8 g (81.2%) of Compound 6. Compound 5A, a mixture of E/Z isomers, can be used in step 5 to prepare Compound 6.

1. additionwere charged to a hydrogenation reactor
2. customwas adjusted to 25° C. to 35° C.
3. customthe reactor was flushed three times with nitrogen (2 bar) and three times with hydrogen (1 bar)
4. temperaturewhile maintaining the hydrogen pressure at 4.5 to 5 bar
5. temperatureThe reaction mixture is then cooled to 40° C. to 50° C
6. filtrationFor the workup, the Pd/C is filtered off
7. customThe aqueous phase was separated
8. additionThe organic phase was treated with activated carbon (5.5 g) for about 10 minutes at 40 to 50° C
9. filtrationThe activated carbon was filtered off
10. customcondensed
11. distillationby distillation
12. temperaturethe resulting suspension was cooled to 15° C. to 20° C. within 2 to 3 hours

ORD record

ord-1710ee4ce18a4f1297049cb290fb745b

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09238673B2