Sodium hydride → 5-Bromo-1-(2-(7-methoxyquinolin-4-yloxy)ethyl)pyridin-2(1H)-one

HRID 1878688Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[CH:4][C:5](=[O:11])[N:6]([CH2:8][CH2:9][OH:10])[CH:7]=1.[H-].[Na+].Cl[C:15]1[C:24]2[C:19](=[CH:20][C:21]([O:25][CH3:26])=[CH:22][CH:23]=2)[N:18]=[CH:17][CH:16]=1>CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5](=[O:11])[N:6]([CH2:8][CH2:9][O:10][C:15]2[C:24]3[C:19](=[CH:20][C:21]([O:25][CH3:26])=[CH:22][CH:23]=3)[N:18]=[CH:17][CH:16]=2)[CH:7]=1

Participants

Conditions

Temperature: 23 °C

Procedure

To a stirring solution of 5-bromo-1-(2-hydroxyethyl)pyridin-2(1H)-one (3000 mg, 13.7 mmol) in DMF (25 mL) was added sodium hydride (60% dispersion in mineral oil, 632.6 mg, 27.5 μmol) portionwise. After stirred for 30 min at 23° C., additional DMF (20 mL) was added to the thick suspension. To this was added 4-chloro-7-methoxyquinoline (2664 mg, 13.7 mmol). Upon completion, the reaction was quenched with 5% NaHCO3 (100 mL), and the aqueous was extracted with CH2Cl2 (4×75 mL). The combined organics were dried over MgSO4, concentrated from toluene, and purified on 80 grams of silica eluting with 30-80% of 5% MeOH/CH2Cl2. The product was isolated as a white solid. MS (ESI pos. ion) m/z (MH+): 375/377. Calc'd exact mass for C17H15BrN2O3: 374. 13C NMR (101 MHz, CDCl3) δ ppm 48.66, 54.80, 64.75, 97.11, 98.75, 106.69, 114.92, 118.10, 121.48, 121.78, 137.81, 142.38, 150.57, 151.00, 159.87, 160.24, 160.40

Workup

customUpon completion, the reaction was quenched with 5% NaHCO3 (100 mL)
extractionthe aqueous was extracted with CH2Cl2 (4×75 mL)
dry with materialThe combined organics were dried over MgSO4
concentrationconcentrated from toluene
custompurified on 80 grams of silica eluting with 30-80% of 5% MeOH/CH2Cl2
customThe product was isolated as a white solid

Sources & evidence

ORD record: ord-3f77a78116654baab77fbda7efc100de
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08314087B2

Reaction notes

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