Dimethyl Sulfoxide → HCID 59536616, 화합물

HRID 1922183노트

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HRID 1922183 반응식
[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

참가 물질

6

반응물 3

HCID 679Dimethyl SulfoxideHCID 23664618Potassium methoxideHCID 59536649HCID 59536649, 화합물

생성물 1

HCID 59536616HCID 59536616, 화합물수율 80%

시약·촉매·용매 2

HCID 962Water용매HCID 15413tert-Butyl methyl ether용매

반응 조건

온도
100 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-ab8577a8569442be8936d6360a63d1d5
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08173821B2

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