Sodium Hydroxide → (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

HRID 591909Notes

Reaction equation

HRID 591909 reaction equation
[OH:1][C@@H:2]1[CH2:25][CH2:24][C@@:23]2([CH3:26])[C@H:4](/[C:5](=[CH:29]/[CH3:30])/[C:6](=[O:28])[C@@H:7]3[C@@H:22]2[CH2:21][CH2:20][C@@:19]2([CH3:27])[C@H:8]3[CH2:9][CH2:10][C@@H:11]2[C@H:12]([CH3:18])[CH2:13][CH2:14][C:15]([OH:17])=[O:16])[CH2:3]1.[OH-].[Na+]>[Pd].O>[OH:1][C@@H:2]1[CH2:25][CH2:24][C@@:23]2([CH3:26])[C@H:4]([C@@H:5]([CH2:29][CH3:30])[C:6](=[O:28])[C@@H:7]3[C@@H:22]2[CH2:21][CH2:20][C@@:19]2([CH3:27])[C@H:8]3[CH2:9][CH2:10][C@@H:11]2[C@H:12]([CH3:18])[CH2:13][CH2:14][C:15]([OH:17])=[O:16])[CH2:3]1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 86706181(R)-4-((3R,5R,8S,9S,10R,13R,14S,17R,Z)-6-ethylidene-3-hydroxy-10,13-dimethyl-7-oxohexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoic acid

Product 1

HCID 67102585(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

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 962WaterSolvent

Procedure

In one embodiment in Step 5, E/Z-3α-hydroxy-6-ethylidene-7-keto-5β-cholan-24-oic acid (5A), water, NaOH solution (e.g. 50% wt.), and Pd/C are mixed at about 5 bar of H2 gas and at a temperature at about 100° C. to about 105° C. until H2 uptake has ceased. The reaction mixture is cooled to about 40° C. to about 50° C. and Pd/C is filtered off. Then n-butyl acetate and HCl are added to the solution containing compound 6. In one embodiment, the aqueous phase is separated and discarded. The organic phase containing compound 6 is treated with activated carbon. The carbon is filtered off and the filtrate is moved to another reactor where it is reduced down by distillation, and then the suspension is cooled to about 5° C. to about 20° C. In one embodiment, compound 6 is isolated via filtration and the filtrate is dried on the pressure filter under vacuum at about 80° C.

Workup

  1. temperatureThe reaction mixture is cooled to about 40° C. to about 50° C.
  2. filtrationPd/C is filtered off
  3. additionThen n-butyl acetate and HCl are added to the solution
  4. additioncontaining compound 6
  5. customIn one embodiment, the aqueous phase is separated
  6. additionThe organic phase containing compound 6
  7. additionis treated with activated carbon
  8. filtrationThe carbon is filtered off
  9. customthe filtrate is moved to another reactor
  10. distillationwhere it is reduced down by distillation
  11. temperaturethe suspension is cooled to about 5° C. to about 20° C

Sources & evidence

ORD record
ord-b7bb239dbb124481bae7f6b6ec432a32
Source dataset
uspto-grants-2016_01
Patent number
US09238673B2

Reaction notes

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