Tetrabutylammonium Fluoride → (1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-9-(3-fluoro-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-carboxylic acid

HRID 85691

Reaktionsgleichung

Reaktionsgleichung von HRID 85691
[F:1][C:2]1[CH:3]=[C:4]([C:12]2[C:13]([CH3:50])([CH3:49])[C@H:14]3[C@:27]([CH3:30])([CH2:28][CH:29]=2)[C@@H:26]2[C@:17]([CH3:48])([C@@:18]4([CH3:47])[C@H:23]([CH2:24][CH2:25]2)[C@H:22]2[C@H:31]([C:34]([CH3:36])=[CH2:35])[CH2:32][CH2:33][C@:21]2([C:37]([O:39]CC2C=CC=CC=2)=[O:38])[CH2:20][CH2:19]4)[CH2:16][CH2:15]3)[CH:5]=[CH:6][C:7]=1[C:8]([O:10][CH3:11])=[O:9].C([SiH](C)C)(C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>ClCCCl.O1CCOCC1.Cl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:1][C:2]1[CH:3]=[C:4]([C:12]2[C:13]([CH3:50])([CH3:49])[C@H:14]3[C@:27]([CH3:30])([CH2:28][CH:29]=2)[C@@H:26]2[C@:17]([CH3:48])([C@@:18]4([CH3:47])[C@H:23]([CH2:24][CH2:25]2)[C@H:22]2[C@H:31]([C:34]([CH3:36])=[CH2:35])[CH2:32][CH2:33][C@:21]2([C:37]([OH:39])=[O:38])[CH2:20][CH2:19]4)[CH2:16][CH2:15]3)[CH:5]=[CH:6][C:7]=1[C:8]([O:10][CH3:11])=[O:9]

Komponenten

8

Edukt 3

HCID 2724141Tetrabutylammonium FluorideHCID 5072427tert-ButyldimethylsilaneHCID 68358212(1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-benzyl 9-(3-fluoro-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

Produkt 1

HCID 68358213(1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-9-(3-fluoro-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-carboxylic acidAusbeute 95 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 167845palladium(II) acetateKatalysatorHCID 111,2-DichloroethaneLösungsmittelHCID 313Hydrochloric AcidLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

To a solution of (1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-benzyl 9-(3-fluoro-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 (3.59 g, 5.27 mmol) in DCE (25 mL) was added TEA (1.176 mL, 8.44 mmol), t-butyldimethylsilane (1.749 mL, 10.54 mmol), and palladium(II) acetate (0.118 g, 0.527 mmol). The mixture was flushed with N2 and heated to 60° C. for 1 h. The mixture was cooled to rt and was filtered through a plug of celite and silica gel (washed with 25% EtOAc in hexanes). The filtrate was concentrated under reduced pressure. The residue was diluted with 25 mL of dioxane and TBAF (75% in water) (2.76 g, 7.91 mmol) was added. The mixture was stirred for 30 minutes at rt then was diluted with 50 mL of 1N HCl. The solids that formed were collected by filtration and were washed with water to give the title compound (2.95 g, 4.99 mmol, 95% yield) as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.83 (1H, t, J=7.9 Hz), 6.90-7.00 (2H, m), 5.34 (1H, dd, J=6.1, 1.6 Hz), 4.77 (1H, d, J=2.0 Hz), 4.64 (1H, s), 3.94 (3H, s), 3.04 (1H, td, J=10.7, 4.8 Hz), 2.24-2.34 (2H, m), 2.13 (1H, dd, J=17.3, 6.3 Hz), 1.96-2.06 (2H, m), 1.72 (3H, s), 1.03 (3H, s), 1.02 (3H, s), 0.98 (3H, s), 0.93-0.96 (6H, m), 0.91-1.80 (17H, m).

Aufarbeitung

  1. customThe mixture was flushed with N2
  2. temperatureThe mixture was cooled to rt
  3. filtrationwas filtered through a plug of celite and silica gel (washed with 25% EtOAc in hexanes)
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. additionwas added
  6. customThe solids that formed
  7. filtrationwere collected by filtration
  8. washwere washed with water

Quellen und Nachweise

ORD-Eintrag
ord-f2453f72483a4e70aba1c5212a340898
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846647B2

Verknüpfte Notizen

Wird geladen…