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Isopropanol → (1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR 13bR)-benzyl 9-(4-(methoxycarbonyl)phenyl)-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]chrysene-3a-carboxylate

HRID 406880
Notes
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Reaction equation

HRID 406880 reaction equation
[CH3:1][C@:2]12[C@@:19]3([CH3:20])[C@@H:10]([C@:11]4([CH3:31])[C@@H:16]([CH2:17][CH2:18]3)[C:15]([CH3:22])([CH3:21])[C:14](OS(C(F)(F)F)(=O)=O)=[CH:13][CH2:12]4)[CH2:9][CH2:8][CH:7]1[C@H:6]1[C@H:32]([C:35]([CH3:37])=[CH2:36])[CH2:33][CH2:34][C@:5]1([C:38]([O:40][CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)=[O:39])[CH2:4][CH2:3]2.CC(O)C.O.C(=O)([O-])[O-].[Na+].[Na+].[CH3:59][O:60][C:61]([C:63]1[CH:68]=[CH:67][C:66](B(O)O)=[CH:65][CH:64]=1)=[O:62]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH3:59][O:60][C:61]([C:63]1[CH:68]=[CH:67][C:66]([C:14]2[C:15]([CH3:22])([CH3:21])[C@H:16]3[C@:11]([CH3:31])([CH2:12][CH:13]=2)[C@@H:10]2[C@:19]([CH3:20])([C@@:2]4([CH3:1])[C@H:7]([CH2:8][CH2:9]2)[C@H:6]2[C@H:32]([C:35]([CH3:37])=[CH2:36])[CH2:33][CH2:34][C@:5]2([C:38]([O:40][CH2:41][C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)=[O:39])[CH2:4][CH2:3]4)[CH2:18][CH2:17]3)=[CH:65][CH:64]=1)=[O:62]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 3776IsopropanolHCID 27343694-Methoxycarbonylphenylboronic acidHCID 2735133Sodium Carbonate MonohydrateHCID 88415331(1R,3aS,5aR,5bR,7aR,11aR,11bR,13bR)-benzyl 5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-9-(trifluoromethylsulfonyloxy)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysene-3a-carboxylate

Product 1

HCID 67776728
(1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR 13bR)-benzyl 9-(4-(methoxycarbonyl)phenyl)-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]chrysene-3a-carboxylate
Yield 68.4%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a round bottom flask containing a solution of (1R,3aS,5aR,5bR,7aR,11aR,11bR,13bR)-benzyl 5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-9-(trifluoromethylsulfonyloxy)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysene-3a-carboxylate (6.21 g, 9.18 mmol) in dioxane (25 mL) was added 2-propanol (25 mL) and water (15 mL) followed by sodium carbonate monohydrate (3.42 g, 27.5 mmol), 4-methoxycarbonylphenylboronic acid (2.478 g, 13.77 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.318 g, 0.275 mmol). The flask was attached to a reflux condenser, was flushed with N2, and was heated to reflux overnight. After heating the mixture for 14.5 h, it was cooled to rt and was diluted with water (75 mL). The mixture was extracted with ethyl acetate (3×75 mL) and washed with brine. The combined organic layers were dried with MgSO4, filtered, and concentrated under reduced pressure. The residue was adsorbed to silica gel and was purified by Biotage flash chromatography using a 0-20% EtOAc in hexanes gradient. The fractions containing the expected product was combined and concentrated under reduced pressure. The expected product, (1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR 13bR)-benzyl 9-(4-(methoxycarbonyl)phenyl)-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]chrysene-3a-carboxylate (4.16 g, 6.28 mmol, 68.4% yield), was isolated as a white foam. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 0.82 (s, 3H), 0.87-1.75 (m, 17H), 0.91 (s, 3H), 0.92 (s, 3H), 0.95 (s, 3H), 0.97 (s, 3H), 1.69 (s, 3H), 1.82-1.95 (m, 2H), 2.09 (dd, J=17.24, 6.26 Hz, 1H), 2.20-2.32 (m, 2H), 3.04 (td, J=10.91, 4.73 Hz, 1H), 3.90 (s, 3H), 4.60 (s, 1H), 4.73 (d, J=1.83 Hz, 1H), 5.07-5.19 (m, 2H), 5.28 (dd, J=6.10, 1.83 Hz, 1H), 7.19 (d, J=8.24 Hz, 2H), 7.29-7.40 (m, 5H), 7.92 (d, J=8.24 Hz, 2H).

Workup

  1. customThe flask was attached to a reflux condenser
  2. customwas flushed with N2
  3. temperaturewas heated
  4. temperatureto reflux overnight
  5. temperatureAfter heating the mixture for 14.5 h
  6. additionwas diluted with water (75 mL)
  7. extractionThe mixture was extracted with ethyl acetate (3×75 mL)
  8. washwashed with brine
  9. dry with materialThe combined organic layers were dried with MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customwas purified by Biotage flash chromatography
  13. additionThe fractions containing the expected product
  14. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-5cec97e01766494caad652be36614696
Source dataset
uspto-grants-2014_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08754068B2

Reaction notes

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