Sodium Hydroxide → 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-carboxycyclopropyl)methylamino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoic acid

HRID 85647Notes

Reaction equation

HRID 85647 reaction equation
C([O:3][C:4]([CH:6]1[CH2:8][CH:7]1[CH2:9][NH:10][C@:11]12[CH2:46][CH2:45][C@@H:44]([C:47]([CH3:49])=[CH2:48])[C@@H:12]1[C@@H:13]1[C@@:26]([CH3:29])([CH2:27][CH2:28]2)[C@@:25]2([CH3:30])[C@@H:16]([C@:17]3([CH3:43])[C@@H:22]([CH2:23][CH2:24]2)[C:21]([CH3:32])([CH3:31])[C:20]([C:33]2[CH:42]=[CH:41][C:36]([C:37]([O:39]C)=[O:38])=[CH:35][CH:34]=2)=[CH:19][CH2:18]3)[CH2:15][CH2:14]1)=[O:5])C.[OH-].[Na+]>O1CCOCC1>[C:4]([CH:6]1[CH2:8][CH:7]1[CH2:9][NH:10][C@:11]12[CH2:46][CH2:45][C@@H:44]([C:47]([CH3:49])=[CH2:48])[C@@H:12]1[C@@H:13]1[C@@:26]([CH3:29])([CH2:27][CH2:28]2)[C@@:25]2([CH3:30])[C@@H:16]([C@:17]3([CH3:43])[C@@H:22]([CH2:23][CH2:24]2)[C:21]([CH3:32])([CH3:31])[C:20]([C:33]2[CH:42]=[CH:41][C:36]([C:37]([OH:39])=[O:38])=[CH:35][CH:34]=2)=[CH:19][CH2:18]3)[CH2:15][CH2:14]1)([OH:5])=[O:3]

Participants

4

Reactant 2

HCID 14798Sodium Hydroxide2×HCID 68358206methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(ethoxycarbonyl)cyclopropyl)methylamino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoate

Product 1

HCID 683581364-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-carboxycyclopropyl)methylamino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoic acidYield 24.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(ethoxycarbonyl)cyclopropyl)methylamino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoate (33 mg, 0.049 mmol) in 1,4-dioxane (2 mL) was added NaOH (1N) (0.246 mL, 0.246 mmol). The mixture was heated to 85° C. for 22 h then was cooled to rt. An additional 0.25 mL of 1N NaOH was added to the mixture and it was again heated to 85° C. After stirring the mixture over the weekend, the reaction mixture was purified by prep HPLC. The fractions containing the expected product were combined and concentrated under reduced pressure. 1H NMR still showed impurities present, so the mixture was purified a second time by prep HPLC. The fractions containing the product were combined and concentrated under reduced pressure to give the title compound (8.3 mg, 0.012 mmol, 24.15% yield) as a white solid. LCMS: m/e 628.6 (M+H)+, 1.66 min (method 2).

Workup

  1. temperaturethen was cooled to rt
  2. temperaturewas again heated to 85° C
  3. customthe reaction mixture was purified by prep HPLC
  4. additionThe fractions containing the expected product
  5. concentrationconcentrated under reduced pressure
  6. customwas purified a second time by prep HPLC
  7. additionThe fractions containing the product
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-1336f174b6844ec9840183393764bd26
Source dataset
uspto-grants-2014_09
Patent number
US08846647B2

Reaction notes

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