Ammonium Chloride → (-)-(6aR,8S,9R,9aR)-9-Fluoro-2,2,4,4-tetraisopropyl-7-methylenehexahydrocyclopenta[f]-[1,3,5,2,4]trioxadisilocin-8-ol

HRID 522821Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 522821
[F:1][C@H:2]1[C@@H:6]2[O:7][Si:8]([CH:22]([CH3:24])[CH3:23])([CH:19]([CH3:21])[CH3:20])[O:9][Si:10]([CH:16]([CH3:18])[CH3:17])([CH:13]([CH3:15])[CH3:14])[O:11][CH2:12][C@H:5]2[C:4](=[CH2:25])[C@H:3]1[OH:26].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.O.O.O.O.O.O.O.[Cl-].[Ce+3].[Cl-].[Cl-].[BH4-].[Na+].[Cl-].[NH4+]>CO.C(O)(=O)C>[F:1][C@H:2]1[C@@H:6]2[O:7][Si:8]([CH:22]([CH3:24])[CH3:23])([CH:19]([CH3:21])[CH3:20])[O:9][Si:10]([CH:16]([CH3:17])[CH3:18])([CH:13]([CH3:14])[CH3:15])[O:11][CH2:12][C@H:5]2[C:4](=[CH2:25])[C@@H:3]1[OH:26]

Komponenten

8

Edukt 5

HCID 25517Ammonium ChlorideHCID 159087TriacetoxyperiodinaneHCID 4311764Sodium borohydrideHCID 21585214Cerium trichloride heptahydrateHCID 131735544(-)-(6aR,8R,9R,9aR)-9-Fluoro-2,2,4,4-tetraisopropyl-7-methylenehexahydrocyclopenta[f]-[1,3,5,2,4]trioxadisilocin-8-ol

Produkt 1

HCID 102334878(-)-(6aR,8S,9R,9aR)-9-Fluoro-2,2,4,4-tetraisopropyl-7-methylenehexahydrocyclopenta[f]-[1,3,5,2,4]trioxadisilocin-8-olAusbeute 86,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 176Acetic AcidLösungsmittelHCID 887MethanolLösungsmittel

Versuchsvorschrift

To a stirred solution of allylic alcohol 14 (5 g, 12.3 mmol) the Dess-martin periodinane reagent (7.8 g, 18.5 mmol) was added at 0° C. The mixture was warm to ambient temperature and stirred for 1 h. Mixture was passed through celite bed and the filtrate was concentrated under reduced pressure to give a crude allylic ketone, which was proceeded as such in next step without further purification. The crude ketone (4.5 g, 11.1 mmol) was dissolved in anhydrous methanol, cooled the solution at −78° C., CeCl3.7H2O (5.5 g, 14.7 mmol) was added at −78° C., and then after 10 minutes stirring, NaBH4 (0.54 g, 14.3 mmol) was added at one portion. After 15 min stirring at −78° C., the reaction mixture was allowed to reach 0° C., saturated solution of ammonium chloride (30 mL) and 10% aqueous solution of acetic acid were added, and then the mixture was allowed for 1 hr while stirring. Organic solvent was removed under reduced pressure and the residue was extracted with DCM (200 ml×2). The combined DCM extracts were washed with brine (50 mL×2), dried (anhydrous Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by flash silica gel column chromatography (5% EtOAc/hexane) to give compound 15 (4.3 g, 86%) as oil. [α]26D −88.1° (c 0.5, MeOH); 1H NMR (500 MHz, CDCl3) δ 0.93-1.08 (m, 28H), 2.66 (s, 1H), 3.89 (dd, J=6.0, 11.5 Hz, 1H), 3.99 (dd, J=4.5, 12.0 Hz, 1H), 4.26-4.21 (m, 1H), 4.47 (dd, J=4.5, 13.5 Hz 1H), 4.65 (dt, J=8.0, 15.0 Hz, 1H), 5.16 (d, J=2.5 Hz, 1H), 5.35 (s, 1H); 19F NMR (500 MHz, CDCl3) δ −195.8 (m); 13C NMR (125 MHz, CDCl3) δ 12.5, 12.7, 13.3, 13.4, 16.9, 16.98, 17.07, 17.08, 17.4, 17.5, 49.1, 63.7, 73.7, 74.7, 102.3 (d, J=192.7 Hz), 111.5, 144.9, 150.0; HR-MS Calcd. For (C19H37FO4Si2+H)+ 405.2214. found 405.2202.

Aufarbeitung

  1. concentrationthe filtrate was concentrated under reduced pressure
  2. customto give a crude allylic ketone, which
  3. customwithout further purification
  4. temperaturecooled the solution at −78° C.
  5. stirringafter 10 minutes stirring
  6. stirringAfter 15 min stirring at −78° C.
  7. customto reach 0° C.
  8. waitthe mixture was allowed for 1 hr
  9. stirringwhile stirring
  10. customOrganic solvent was removed under reduced pressure
  11. extractionthe residue was extracted with DCM (200 ml×2)
  12. washThe combined DCM extracts were washed with brine (50 mL×2)
  13. dry with materialdried (anhydrous Na2SO4)
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure
  16. customThe residue was purified by flash silica gel column chromatography (5% EtOAc/hexane)

Quellen und Nachweise

ORD-Eintrag
ord-ab7082dfb06c417ab4ab7a7e689e625c
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09334273B1

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