Dimethyl Sulfoxide → HCID 59536616、化合物

HRID 1922183ノート

反応式

HRID 1922183 の反応式
[CH2:1]([N:8]1[CH2:12][CH2:11][C@H:10]([C@@H:13]([O:18][C:19]2[C:20]([CH3:26])=[N:21][C:22](Cl)=[CH:23][CH:24]=2)[CH2:14][CH:15]([CH3:17])[CH3:16])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CS(C)=O.[CH3:31][O-:32].[K+]>O.CC(OC)(C)C>[CH2:1]([N:8]1[CH2:12][CH2:11][C@H:10]([C@@H:13]([O:18][C:19]2[C:20]([CH3:26])=[N:21][C:22]([O:32][CH3:31])=[CH:23][CH:24]=2)[CH2:14][CH:15]([CH3:17])[CH3:16])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

6

反応物 3

HCID 679Dimethyl SulfoxideHCID 23664618Potassium methoxideHCID 59536649HCID 59536649、化合物

生成物 1

HCID 59536616HCID 59536616、化合物収率 80%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 15413tert-Butyl methyl ether溶媒

反応条件

温度
100 °C

実験手順

To a 200 mL RB flask equipped with a magnetic stir bar and N2 inlet was charged with (S)-1-benzyl-3-((S)-1-(6-chloro-2-methyl-3-pyridyloxy)-3-methylbutyl)-pyrrolidine (5.46 g, 14.65 mmoles) and DMSO (30 mL). Add potassium methoxide (4.11 g, 58.61 mmoles) in one portion with stirring. Stir the reaction mixture in an oil bath at 100° C. for 1 hour. Dilute with H2O (60 mL) and MTBE (60 mL). Separate the layers and wash organic layer with H2O (2×30 mL), followed by brine (30 mL), and then dry over Na2SO4. Filter and concentrate the crude material (in toluene). Load onto silica (225 g, wet with toluene), and elute with the following: hexanes (2×500 mL), 50% MTBE/hexanes (6×500 mL). Concentrate the appropriate fractions to give (S)-1-benzyl-3-((S)-1-(6-methoxy-2-methyl-3-pyridyloxy)-3-methylbutyl)-pyrrolidine. (4.32 g, 11.72 mmoles, 80% yield) as a yellow/orange oil. 1H NMR (300 MHz, CDCl3) δ 7.34-7.2 (m, 5H), 7.10 (d, 1H, J=8.79 Hz), 6.49 (d, 1H, J=8.79), 4.17-4.07 (m, 1H), 3.88 (s, 3H), 3.68-3.50 (m, 2H), 2.78-2.67 (m, 2H), 2.61-2.48 (m, 1H), 2.48-2.38 (m, 1H), 2.37 (s, 3H), 2.33-2.24 (m, 1H), 2.00-1.50 (m, 5H), 1.44-1.30 (m, 1H), 0.885 (at, 6H, Ja=7.03 Hz, Jb=6.44 Hz). LC/MS=369.3 (M+1).

後処理

  1. customTo a 200 mL RB flask equipped with a magnetic stir bar and N2 inlet
  2. customSeparate the layers
  3. washwash organic layer with H2O (2×30 mL)
  4. dry with materialdry over Na2SO4
  5. filtrationFilter
  6. concentrationconcentrate the crude material (in toluene)
  7. washLoad onto silica (225 g, wet with toluene), and elute with the following: hexanes (2×500 mL), 50% MTBE/hexanes (6×500 mL)
  8. concentrationConcentrate the appropriate fractions

出典と根拠

ORDレコード
ord-ab8577a8569442be8936d6360a63d1d5
出典データセット
uspto-grants-2012_05
特許番号
US08173821B2

反応ノート

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