Sodium hydride → {1-[2-(7-Methoxy-quinoxalin-2-yloxy)-ethyl]-piperidin-4-yl}-carbamic acid tert-butyl ester

HRID 1019849Notes

Reaction equation

HRID 1019849 reaction equation
[H-].[Na+].Cl[C:4]1[CH:13]=[N:12][C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[CH:9][CH:10]=2)[N:5]=1.[C:16]([O:20][C:21](=[O:32])[NH:22][CH:23]1[CH2:28][CH2:27][N:26]([CH2:29][CH2:30][OH:31])[CH2:25][CH2:24]1)([CH3:19])([CH3:18])[CH3:17]>CN(C)C=O>[C:16]([O:20][C:21](=[O:32])[NH:22][CH:23]1[CH2:24][CH2:25][N:26]([CH2:29][CH2:30][O:31][C:4]2[CH:13]=[N:12][C:11]3[C:6](=[CH:7][C:8]([O:14][CH3:15])=[CH:9][CH:10]=3)[N:5]=2)[CH2:27][CH2:28]1)([CH3:19])([CH3:17])[CH3:18]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 126864152-Chloro-7-methoxyquinoxalineHCID 45076484[1-(2-Hydroxy-ethyl)-piperidin-4-yl]-carbamic acid tert-butyl ester

Product 1

HCID 66747403{1-[2-(7-Methoxy-quinoxalin-2-yloxy)-ethyl]-piperidin-4-yl}-carbamic acid tert-butyl esterYield 52.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (55% purity, 62 mg, 1.48 mmol, 1.5 eq) is added at room temperature to a stirred solution of 2-chloro-7-methoxy-quinoxaline (200 mg, 0.99 mmol, 1.0 eq) in N,N-dimethylformamide (10 mL), followed by [1-(2-hydroxy-ethyl)-piperidin-4-yl]-carbamic acid tert-butyl ester (268 mg, 0.99 mmol, 1.0 eq). After 4 hours stirring at room temperature, solvent is evaporated, and the residue is extracted with dichloromethane (3×20 mL) and water (20 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated to give a residue that is purified by column chromatography (silica gel, eluent: cyclohexane:ethyl acetate:methanol, 1:1:0 to 0:9:1, v/v/v) to afford {1-[2-(7-methoxy-quinoxalin-2-yloxy)-ethyl]-piperidin-4-yl}-carbamic acid tert-butyl ester as an orange solid (210 mg, 52% yield).

Workup

  1. customsolvent is evaporated
  2. extractionthe residue is extracted with dichloromethane (3×20 mL) and water (20 mL)
  3. dry with materialThe combined organic layers are dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a residue that
  7. customis purified by column chromatography (silica gel, eluent: cyclohexane:ethyl acetate:methanol, 1:1:0 to 0:9:1, v/v/v)

Sources & evidence

ORD record
ord-f4b852c62c994aae87990d7d01d4da28
Source dataset
uspto-grants-2014_05
Patent number
US08716280B2

Reaction notes

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