Dimethylformamide → 3-Chloro-6-methoxyquinoline-4-carbaldehyde

HRID 633827Notes

Reaction equation

C([Li])CCC.Br[C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:17][CH3:18])[CH:15]=2)[N:10]=[CH:9][C:8]=1[Cl:19].CN(C)[CH:22]=[O:23].C(OCC)(=O)C>O1CCCC1>[Cl:19][C:8]1[CH:9]=[N:10][C:11]2[C:16]([C:7]=1[CH:22]=[O:23])=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2

Participants

Conditions

Temperature: -78 °C

Procedure

A solution of n-butyllithium (1.6 M in tetrahydrofuran, 0.46 mL, 0.73 mmol, 1.0 eq) is added at −78° C. to a stirred solution of 4-bromo-3-chloro-6-methoxy-quinoline (200 mg, 0.73 mmol, 1.0 eq) in tetrahydrofuran (10 mL). After 2 hours stirring at −78° C., N,N-dimethylformamide (0.3 mL) is added and the reaction mixture is stirred at 60° C. for two hours. Then solvent is evaporated and the residue is extracted with ethyl acetate (3×10 mL) and water (10 mL). The combined organic layers are washed with brine, dried over sodium sulfate, filtered and concentrated to give a crude product that is purified by column chromatography (silica gel, eluent: petroleum ether:ethyl acetate, 5:1, v/v) to afford 3-chloro-6-methoxy-quinoline-4-carbaldehyde as a light yellow solid (78 mg, 48% yield).

Workup

stirringthe reaction mixture is stirred at 60° C. for two hours
customThen solvent is evaporated
extractionthe residue is extracted with ethyl acetate (3×10 mL) and water (10 mL)
washThe combined organic layers are washed with brine
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customto give a crude product that
customis purified by column chromatography (silica gel, eluent

Sources & evidence

ORD record: ord-1ca37bc8561946d4a5093823e20308e9
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09321788B2

Reaction notes

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