Dimethyl Sulfoxide → HCID 59536616, compound

HRID 1922183Notes

Reaction equation

HRID 1922183 reaction equation
[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

Participants

6

Reactant 3

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

Product 1

HCID 59536616HCID 59536616, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
100 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-ab8577a8569442be8936d6360a63d1d5
Source dataset
uspto-grants-2012_05
Patent number
US08173821B2

Reaction notes

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