Sodium hydride → 2-(4-((3-Chloropyrazin-2-yl)oxy)piperidin-1-yl)quinoline

HRID 454878Notes

Reaction equation

HRID 454878 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[N:11]1[CH2:16][CH2:15][CH:14]([OH:17])[CH2:13][CH2:12]1.[H-].[Na+].[Cl:20][C:21]1[C:26](Cl)=[N:25][CH:24]=[CH:23][N:22]=1>CN(C=O)C.O>[Cl:20][C:21]1[C:26]([O:17][CH:14]2[CH2:13][CH2:12][N:11]([C:2]3[CH:3]=[CH:4][C:5]4[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=4)[N:1]=3)[CH2:16][CH2:15]2)=[N:25][CH:24]=[CH:23][N:22]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 785752,3-DichloropyrazineHCID 405164181-(2-quinolinyl)-4-Piperidinol

Product 1

HCID 585476872-(4-((3-Chloropyrazin-2-yl)oxy)piperidin-1-yl)quinolineYield 70%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(quinolin-2-yl)piperidin-4-ol (see PREPARATION P1.1; 2.0 g, 8.7 mmol) in DMF (30 mL) at room temperature was added sodium hydride (60% wt in mineral oil) (0.47 g, 17.4 mmol) at 0° C. The mixture was stirred at room temperature for 60 min and then 2,3-dichloro-pyrazine (1.2 g, 8.7 mmol) was added. The reaction mixture was heated to 90° C. overnight and then diluted with water (60 mL) and extracted with EtOAc (2×50 mL). The combined organic extracts were washed with water (40 mL) and brine (40 mL), dried over Na2SO4, and filtered. The filtrate was evaporated in vacuo and the residue was purified by flash column chromatography on silica gel (10% to 30% EtOAc in petroleum ether) to give the title product (2.0 g, 5.8 mmol, 70% yield) as white solid. ESI-MS (M+1): 341 calc. for C18H12ClN4O 340.

Workup

  1. temperatureThe reaction mixture was heated to 90° C. overnight
  2. extractionextracted with EtOAc (2×50 mL)
  3. washThe combined organic extracts were washed with water (40 mL) and brine (40 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customThe filtrate was evaporated in vacuo
  7. customthe residue was purified by flash column chromatography on silica gel (10% to 30% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-2bbd35d4726e4a398a8236d86bb698cb
Source dataset
uspto-grants-2013_07
Patent number
US08497265B2

Reaction notes

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