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

HRID 428874ノート

反応式

HRID 428874 の反応式
[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

参加物

8

反応物 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

生成物 2

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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
50 °C

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-a7f91e75648b413bac35083688aa2f7c
出典データセット
uspto-grants-2001_11
特許番号
US06313312B1

反応ノート

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