Acetic Acid → Deoxycholic Acid Impurity 39

HRID 1748232Notes

Reaction equation

HRID 1748232 reaction equation
C([O:4][C@@H:5]1[CH2:29][CH2:28][C@@:27]2([CH3:30])[C@H:7]([CH2:8][CH2:9][C@@H:10]3[C:26]2=[CH:25][CH2:24][C@@:23]2([CH3:31])[C@H:11]3[CH2:12][CH2:13][C@@H:14]2[C@H:15]([CH3:22])[CH2:16][CH2:17][C:18]([O:20][CH3:21])=[O:19])[CH2:6]1)(=O)C.CC(O)=[O:34]>>[OH:4][C@@H:5]1[CH2:29][CH2:28][C@@:27]2([CH3:30])[C@H:7]([CH2:8][CH2:9][C@@H:10]3[C:26]2=[CH:25][C:24](=[O:34])[C@@:23]2([CH3:31])[C@H:11]3[CH2:12][CH2:13][C@@H:14]2[C@H:15]([CH3:22])[CH2:16][CH2:17][C:18]([O:20][CH3:21])=[O:19])[CH2:6]1

Participants

3

Reactant 2

HCID 176Acetic AcidHCID 59365567(R)-Methyl 4-((3R,5R,8S,10S,13R,14S,17R)-3-acetoxy-10,13-dimethyl-2,3,4,5,6,7,8,10,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoate

Product 1

HCID 255793Deoxycholic Acid Impurity 39Yield 50%

Conditions

Temperature
50 °C

Procedure

CrO3 (17.0 g, 170 mmol) was added to a solution of compound 1.8a (17 g, 39.5 mmol) in AcOH (270 mL). The resulting mixture was heated at 50° C. for 24-36 h. Upon complete disappearance of the starting material by TLC, the solvent was evaporated under vacuum and the crude material was dissolved in ethyl acetate (400 mL) and water (200 mL). The two phases were separated and the organic layer was washed twice with water (2×100 mL) and then once with saturated brine solution (100 mL). The organic phase was dried over anhydrous Na2SO4 (40 g) and filtered. The filtrate was concentrated under vacuum and the resulting solid was purified by column chromatography [49 mm (W)×600 mm (L), 60-120 mesh silica, 120 g], eluting with ethyl acetate/hexane (1:5) [10 mL fractions, 3 mL/min elution, monitored by TLC and detected with UV light (254 nm) lamp]. The product-containing fractions were combined and concentrated under vacuum to afford compound 1.9a (8.8 g, 50% yield) as a white solid.

Workup

  1. customUpon complete disappearance of the starting material by TLC, the solvent was evaporated under vacuum
  2. dissolutionthe crude material was dissolved in ethyl acetate (400 mL)
  3. customThe two phases were separated
  4. washthe organic layer was washed twice with water (2×100 mL)
  5. dry with materialThe organic phase was dried over anhydrous Na2SO4 (40 g)
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated under vacuum
  8. customthe resulting solid was purified by column chromatography [49 mm (W)×600 mm (L), 60-120 mesh silica, 120 g]
  9. washeluting with ethyl acetate/hexane (1:5) [10 mL fractions, 3 mL/min elution, monitored by TLC and detected with UV light (254 nm) lamp]
  10. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-ddf76f05462c4e8795fd61275b3a5908
Source dataset
uspto-grants-2015_10
Patent number
US09150607B2

Reaction notes

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