Diethyl Ether → N-{3-[3-(3-Cyclohexyl-3-hydroxypropyl)-6-methyl-3-azabicyclo[3.1.0]hex-6-yl]phenyl}methanesulfonamide

HRID 428874Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 428874
[CH3:1][C:2]1([C:8]2[CH:9]=[C:10]([NH:14][S:15]([CH3:18])(=[O:17])=[O:16])[CH:11]=[CH:12][CH:13]=2)[CH:7]2[CH:3]1[CH2:4][NH:5][CH2:6]2.Cl.C(=O)([O-])O.[Na+].BrC1C=CC(S(O[CH2:36][CH2:37][C@@H:38]([CH:40]2[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]2)[OH:39])(=O)=O)=CC=1.C(OCC)C>CN(C)C=O.O>[NH3:5].[CH:40]1([CH:38]([OH:39])[CH2:37][CH2:36][N:5]2[CH2:6][CH:7]3[CH:3]([C:2]3([C:8]3[CH:9]=[C:10]([NH:14][S:15]([CH3:18])(=[O:17])=[O:16])[CH:11]=[CH:12][CH:13]=3)[CH3:1])[CH2:4]2)[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]1

Komponenten

8

Edukt 4

HCID 3283Diethyl EtherHCID 516892Sodium BicarbonateHCID 10643291(S)-3-cyclohexyl-3-hydroxypropyl 4-bromobenzenesulfonateHCID 22141325N-[3-(6-methyl-3-azabicyclo[3.1.0]hex-6-yl)phenyl]methanesulfonamide hydrochloride salt

Produkt 2

HCID 222AmmoniaHCID 9909306N-{3-[3-(3-Cyclohexyl-3-hydroxypropyl)-6-methyl-3-azabicyclo[3.1.0]hex-6-yl]phenyl}methanesulfonamideAusbeute 25 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

To a solution of hydrochloride salt N-[3-(6-methyl-3-azabicyclo[3.1.0]hex-6-yl)phenyl]methanesulfonamide (Preparation 53, 200 mg, 0.66 mmol) in N,N-dimethylformamide (8 ml) was added sodium hydrogen carbonate (3 g, 36 mmol) and (S)-3-cyclohexyl-3-hydroxypropyl 4-bromobenzenesulfonate (J. A. Werner et al, J. Org. Chem., 1996, 61, 587) (0.08 ml, 0.89 mmol) and the reaction mixture was heated at 50° C. for 20 h. After cooling, diethyl ether (15 ml) and water (15 ml) were added and the reaction mixture was stirred vigorously for 5 min. The phases were separated and the aqueous layer was further extracted with diethyl ether (2×15 ml). The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo. The residual oil was purified by flash column chromatography using a Sep-Pak™ cartridge packed with silica gel (10 g) eluting with dichloromethane:ethanol:0.88 ammonia solution (200:8:1) to afford the title compound as an oil (90 mg, 25%).

Aufarbeitung

  1. temperatureAfter cooling
  2. customThe phases were separated
  3. extractionthe aqueous layer was further extracted with diethyl ether (2×15 ml)
  4. dry with materialThe combined organic extracts were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residual oil was purified by flash column chromatography
  8. washeluting with dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-a7f91e75648b413bac35083688aa2f7c
Quelldatensatz
uspto-grants-2001_11
Patentnummer
US06313312B1

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