Dimethyl Sulfoxide → 6-Methoxy-8-[2-(3-naphthalen-2-yl-8-azabicyclo[3.2.1]oct-2-en-8-yl)-ethoxy]-quinoline

HRID 987579Notes

Reaction equation

HRID 987579 reaction equation
Cl[CH2:2][CH2:3][N:4]1[CH:9]2[CH2:10][CH2:11][CH:5]1[CH:6]=[C:7]([C:12]1[CH:21]=[CH:20][C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:13]=1)[CH2:8]2.[CH3:22][O:23][C:24]1[CH:25]=[C:26]2[C:31](=[C:32]([OH:34])[CH:33]=1)[N:30]=[CH:29][CH:28]=[CH:27]2.[H-].[Na+].CS(C)=O>CCO.O>[CH3:22][O:23][C:24]1[CH:25]=[C:26]2[C:31](=[C:32]([O:34][CH2:2][CH2:3][N:4]3[CH:9]4[CH2:10][CH2:11][CH:5]3[CH:6]=[C:7]([C:12]3[CH:21]=[CH:20][C:19]5[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=5)[CH:13]=3)[CH2:8]4)[CH:33]=1)[N:30]=[CH:29][CH:28]=[CH:27]2

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 24758Sodium hydrideHCID 180091706-Methoxyquinolin-8-olHCID 180091818-(2-Chloroethyl)-3-(2-naphthyl)-8-azabicyclo[3.2.1]oct-2-ene

Product 1

HCID 102967556-Methoxy-8-[2-(3-naphthalen-2-yl-8-azabicyclo[3.2.1]oct-2-en-8-yl)-ethoxy]-quinolineYield 38%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

8-(2-Chloroethyl)-3-(2-naphthyl)-8-azabicyclo[3.2.1]oct-2-ene (0.50 g, 1.70 mmol), 0.39 g (2.20 mmol) 6-methoxyquinolin-8-ol, 0.08 g (2.00 mmol) NaH (60% dispersion in mineral oil) and 3 mL DMSO are stirred at 50 C for 16 h. The reaction mixture is poured into 100 mL of H2O and extracted with 3×50 mL EtOAc. The combined organics are washed with 3×100 mL H2O, 1×100 mL brine, dried over MgSO4, filtered, and the volatiles are evaporated. The crude product is subjected to flash chromatography on SiO2 gel, eluting with EtOAc and then 40/1 EtOAc/2M NH3 in MeOH, to produce an off-white solid. This solid is treated with 0.06 g (0.67 mmol) (CO2H)2 in 4 mL of absolute EtOH to give 0.33 g (0.13 mmol, a 38% yield) of the oxalate salt of the title compound as a white solid. mp: 100-103° C.; MS (ES) m/z 437 (MH)+.

Workup

  1. extractionextracted with 3×50 mL EtOAc
  2. washThe combined organics are washed with 3×100 mL H2O, 1×100 mL brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customthe volatiles are evaporated
  6. washeluting with EtOAc
  7. custom40/1 EtOAc/2M NH3 in MeOH, to produce an off-white solid
  8. customto give 0.33 g (0.13 mmol

Sources & evidence

ORD record
ord-81263b350d7f4000a7d2492b05504210
Source dataset
uspto-grants-2003_10
Patent number
US06632824B2

Reaction notes

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