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

HRID 1826371노트

반응식

HRID 1826371 반응식
[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.C(=O)([O-])O.[Na+].BrC1C=CC(S(O[CH2:35][CH2:36][C@@H:37]([CH:39]2[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]2)[OH:38])(=O)=O)=CC=1.C(OCC)C>CN(C)C=O.O>[NH3:5].[CH:39]1([CH:37]([OH:38])[CH2:36][CH2:35][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)[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]1

참가 물질

8

반응물 4

HCID 3283Diethyl EtherHCID 516892Sodium BicarbonateHCID 10643291(S)-3-cyclohexyl-3-hydroxypropyl 4-bromobenzenesulfonateHCID 22141143N-[3-(6-methyl-3-azabicyclo[3.1.0]hex-6-yl)phenyl)methanesulfonamide

생성물 2

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

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

반응 조건

온도
50 °C

실험 절차

To a solution of the hydrochloride salt of 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%).

후처리

  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

출처 및 근거

ORD 기록
ord-e4c90a56db2f41478be797157cead1d6
출처 데이터셋
uspto-grants-2006_05
특허 번호
US07049444B2

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