(8R)-2-Methyl-7,8-dihydro[1,4]dioxino[2,3-g][1,3]benzoxazol-8-ylmethyl 4-methylbenzenesulfonate → 8-{[2-Methyl-7,8-dihydro[1,4]dioxino[2,3-g][1,3]benzoxazol-8-yl]methyl}-3-phenyl-8-azabicyclo[3.2.1]octan-3-ol

HRID 130395

Reaktionsgleichung

Reaktionsgleichung von HRID 130395
CC1C=CC(S(O[CH2:12][C@H:13]2[CH2:26][O:25][C:16]3[CH:17]=[CH:18][C:19]4[N:20]=[C:21]([CH3:24])[O:22][C:23]=4[C:15]=3[O:14]2)(=O)=O)=CC=1.[C:27]1([C:33]2([OH:41])[CH2:39][CH:38]3[NH:40][CH:35]([CH2:36][CH2:37]3)[CH2:34]2)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>CS(C)=O.C(OCC)(=O)C>[CH3:24][C:21]1[O:22][C:23]2[C:15]3[O:14][CH:13]([CH2:12][N:40]4[CH:38]5[CH2:37][CH2:36][CH:35]4[CH2:34][C:33]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)([OH:41])[CH2:39]5)[CH2:26][O:25][C:16]=3[CH:17]=[CH:18][C:19]=2[N:20]=1

Komponenten

5

Edukt 2

HCID 11245807(8R)-2-Methyl-7,8-dihydro[1,4]dioxino[2,3-g][1,3]benzoxazol-8-ylmethyl 4-methylbenzenesulfonateHCID 130912463-Phenyl-8-azabicyclo[3.2.1]octan-3-ol

Produkt 1

HCID 102013708-{[2-Methyl-7,8-dihydro[1,4]dioxino[2,3-g][1,3]benzoxazol-8-yl]methyl}-3-phenyl-8-azabicyclo[3.2.1]octan-3-ol

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 679Dimethyl SulfoxideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
77.5 °C

Versuchsvorschrift

(8R)-2-Methyl-7,8-dihydro[1,4]dioxino[2,3-g][1,3]benzoxazol-8-ylmethyl 4-methylbenzenesulfonate (0.375 g, 1.00 mmole) and 3-phenyl-8-aza-bicyclo[3.2.1]-octan-3-ol (0.25 g, 1.2 mmole) were combined in 8 mL of DMSO. This solution was heated to 75-80° C. under nitrogen for 8 hours. After completion, the reaction was cooled to room temperature and diluted to 500 mL with ethyl acetate. The mixture was washed twice with 400 mL portions of saturated aqueous sodium bicarbonate, with 300 mL of water and twice with 400 mL of saturated brine, dried over sodium sulfate, filtered and concentrated in vacuum. The crude oil was column chromatographed on silica gel using first methylene chloride to remove impurities and then 0.5% methanol/methylene chloride to give, after concentration of the product fractions in vacuum, 0.12 g of the (S)-enantiomer of the title compound as an off-white solid, m.p. 203-205° C.

Aufarbeitung

  1. temperatureAfter completion, the reaction was cooled to room temperature
  2. washThe mixture was washed twice with 400 mL portions of saturated aqueous sodium bicarbonate, with 300 mL of water and twice with 400 mL of saturated brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuum
  6. customchromatographed on silica gel using first methylene chloride
  7. customto remove impurities
  8. custom0.5% methanol/methylene chloride to give

Quellen und Nachweise

ORD-Eintrag
ord-04405629bb87446194b52ecd67069589
Quelldatensatz
uspto-grants-2008_06
Patentnummer
US07381723B2

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