Trifluoroacetic acid → HCID 71596782, compound

HRID 405067Notes

Reaction equation

HRID 405067 reaction equation
[CH3:1][C@:2]12[C@@:19]3([CH3:20])[C@@H:10]([C@:11]4([CH3:36])[C@@H:16]([CH2:17][CH2:18]3)[C:15]([CH3:22])([CH3:21])[C:14]([C:23]3[CH:35]=[CH:34][C:26]([C:27]([O:29]C(C)(C)C)=[O:28])=[CH:25][CH:24]=3)=[CH:13][CH2:12]4)[CH2:9][CH2:8][C@@H:7]1[C@H:6]1[C@H:37]([C:40]([CH3:42])=[CH2:41])[CH2:38][CH2:39][C@:5]1([CH2:43][NH:44][CH2:45][CH2:46][N:47]1[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48]1)[CH2:4][CH2:3]2.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:1][C@:2]12[C@@:19]3([CH3:20])[C@@H:10]([C@:11]4([CH3:36])[C@@H:16]([CH2:17][CH2:18]3)[C:15]([CH3:21])([CH3:22])[C:14]([C:23]3[CH:24]=[CH:25][C:26]([C:27]([OH:29])=[O:28])=[CH:34][CH:35]=3)=[CH:13][CH2:12]4)[CH2:9][CH2:8][C@@H:7]1[C@H:6]1[C@H:37]([C:40]([CH3:42])=[CH2:41])[CH2:38][CH2:39][C@:5]1([CH2:43][NH:44][CH2:45][CH2:46][N:47]1[CH2:48][CH2:49][CH2:50][CH2:51][CH2:52]1)[CH2:4][CH2:3]2

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86676407HCID 86676407, compound

Product 1

HCID 71596782HCID 71596782, compoundYield 52.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((2-(piperidin-1-yl)ethylamino)methyl)-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 (119 mg, 0.167 mmol) in DCM (1 ml) was added TFA (0.4 ml, 5.19 mmol). The mixture was stirred at rt for 6 h then was concentrated under reduced pressure. The residue was dissolved in dioxane and MeOH and was purified by prep HPLC. The fractions containing the expected product were combined and concentrated under reduced pressure. The residue was dissolved in dioxane and methanol and the mixture was heated with a heat gun to reflux. Water was slowly added until the mixture was slightly cloudy. The mixture was allowed to cool to rt and then was refrigerated overnight. The solids that formed were collected by filtration and were washed with water to afford the title compound as a light-yellow solid (57 mg, 0.087 mmol, 52.1% yield). LCMS: m/e 655.6 (M+H)+, 2.28 min (method 6). 1H NMR (400 MHz, Acetic Acid d4) δ ppm 7.99 (d, J=8.28 Hz, 2H), 7.25 (d, J=8.28 Hz, 2H), 5.32 (d, J=4.52 Hz, 1H), 4.75 (s, 1H), 4.63 (s, 1H), 3.72 (s, 2H), 3.56-3.66 (m, 2H), 3.33 (d, J=12.80 Hz, 1H), 2.98 (d, J=12.80 Hz, 1H), 2.48 (br. s., 1H), 1.71 (s, 3H), 1.14 (s, 3H), 1.09-2.22 (m, 32H), 1.05 (s, 3H), 1.03 (s, 3H), 0.97 (s, 3H), 0.96 (s, 3H).

Workup

  1. concentrationthen was concentrated under reduced pressure
  2. dissolutionThe residue was dissolved in dioxane
  3. customMeOH and was purified by prep HPLC
  4. additionThe fractions containing the expected product
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe residue was dissolved in dioxane
  7. temperaturemethanol and the mixture was heated with a heat gun
  8. temperatureto reflux
  9. additionWater was slowly added until the mixture
  10. temperatureto cool to rt
  11. waitwas refrigerated overnight
  12. customThe solids that formed
  13. filtrationwere collected by filtration
  14. washwere washed with water

Sources & evidence

ORD record
ord-068f2d7b62574098967536a47be301c0
Source dataset
uspto-grants-2014_06
Patent number
US08748415B2

Reaction notes

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