Sodium hydride → 1-(2-(7-Methoxyquinolin-4-yloxy)ethyl)-5-phenylpiperidin-2-one

HRID 1878730Notes

Reaction equation

HRID 1878730 reaction equation
[OH:1][CH2:2][CH2:3][N:4]1[CH2:9][CH:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:7][CH2:6][C:5]1=[O:16].[H-].[Na+].Cl[C:20]1[C:29]2[C:24](=[CH:25][C:26]([O:30][CH3:31])=[CH:27][CH:28]=2)[N:23]=[CH:22][CH:21]=1>CN(C=O)C>[CH3:31][O:30][C:26]1[CH:25]=[C:24]2[C:29]([C:20]([O:1][CH2:2][CH2:3][N:4]3[CH2:9][CH:8]([C:10]4[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=4)[CH2:7][CH2:6][C:5]3=[O:16])=[CH:21][CH:22]=[N:23]2)=[CH:28][CH:27]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 106078294-Chloro-7-methoxyquinolineHCID 598430141-(2-Hydroxyethyl)-5-phenylpiperidin-2-one

Product 1

HCID 598430541-(2-(7-Methoxyquinolin-4-yloxy)ethyl)-5-phenylpiperidin-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
23 °C

Procedure

To a stirring solution of 1-(2-hydroxyethyl)-5-phenylpiperidin-2-one (100 mg, 456 μmol) in DMF (1.5 mL) under nitrogen was added NaH (60% dispersion in mineral oil; 16 mg, 684 μmol). The suspension was stirred for 10 min at 23° C., then 4-chloro-7-methoxyquinoline (132 mg, 684 μmol) was added. After 2 h at 23° C. the reaction mixture was partitioned between CH2Cl2 (15 mL) and 5% NaHCO3 (10 mL). The aqueous was extracted with CH2Cl2 (5 mL) twice. The organics were dried over MgSO4, concentrated to a solid from toluene under reduced pressure. Purification on silica (12 g) eluting with 10>40% of 5% MeOH/CH2Cl2 afforded a white solid from acetonitrile. 1H NMR (400 MHz, Chloroform-d) δ ppm 1.95-2.09 (m, 2 H) 2.40-2.64 (m, 2 H) 2.97-3.09 (m, 1H) 3.63 (t, J=11.35 Hz, 1 H) 3.68-3.76 (m, 1 H) 3.88 (t, J=4.99 Hz, 2 H) 3.94 (s, 3 H) 4.36-4.47 (m, 2 H) 6.65 (d, J=5.28 Hz, 1 H) 7.08 (dd, J=9.19, 2.54 Hz, 1 H) 7.16 (d, J=6.85 Hz, 2 H) 7.22-7.34 (m, 3 H) 7.38 (d, J=2.35 Hz, 1 H) 7.96 (d, J=9.00 Hz, 1 H) 8.66 (d, J=5.28 Hz, 1 H).

Workup

  1. customAfter 2 h at 23° C. the reaction mixture was partitioned between CH2Cl2 (15 mL) and 5% NaHCO3 (10 mL)
  2. extractionThe aqueous was extracted with CH2Cl2 (5 mL) twice
  3. dry with materialThe organics were dried over MgSO4
  4. concentrationconcentrated to a solid from toluene under reduced pressure
  5. customPurification on silica (12 g)
  6. washeluting with 10>40% of 5% MeOH/CH2Cl2
  7. customafforded a white solid from acetonitrile

Sources & evidence

ORD record
ord-38e19c93e8b44de9a3274cb1f625b281
Source dataset
uspto-grants-2012_11
Patent number
US08314087B2

Reaction notes

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