Diethyl Malonate → 2-(7-Fluoro-2-methoxy-quinolin-8-ylmethyl)-malonic acid diethyl ester

HRID 1801466Notes

Reaction equation

[H-].[Na+].[C:3]([O:11][CH2:12][CH3:13])(=[O:10])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].Br[CH2:15][C:16]1[C:17]([F:28])=[CH:18][CH:19]=[C:20]2[C:25]=1[N:24]=[C:23]([O:26][CH3:27])[CH:22]=[CH:21]2>C1COCC1>[CH2:12]([O:11][C:3](=[O:10])[CH:4]([CH2:15][C:16]1[C:17]([F:28])=[CH:18][CH:19]=[C:20]2[C:25]=1[N:24]=[C:23]([O:26][CH3:27])[CH:22]=[CH:21]2)[C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH3:13]

Participants

Conditions

Temperature: 0 °C

Procedure

To a suspension of NaH (60% dispersion in oil, 0.88 g, 22 mmol) in THF (100 mL), was added diethyl malonate (3.79 g, 23.66 mmol). The reaction mixture was cooled to 0° C. and 8-bromomethyl-7-fluoro-2-methoxy-quinoline (5.4 g, 20 mmol) was added in one portion. The reaction proceeded 30 min at 0° C. and 15 min at rt. The reaction mixture was quenched by adding water (20 mL) and 10% NaHSO4 (100 mL). The two layers were decanted and the aq. layer was extracted once with EA (100 mL). The combined org. layers were washed with brine, dried over Na2SO4, filtered and concentrated to dryness. The residue was purified by CC (Hept-EA 4:1) to afford the title compound as a yellowish oil (6.4 g). The product was contaminated with 20% of diethyl malonate.

Workup

customThe reaction mixture was quenched
additionby adding water (20 mL) and 10% NaHSO4 (100 mL)
customThe two layers were decanted
extractionthe aq. layer was extracted once with EA (100 mL)
washlayers were washed with brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated to dryness
customThe residue was purified by CC (Hept-EA 4:1)

Sources & evidence

ORD record: ord-0cbad0468cee4fd89da054744d5cfaab
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08349828B2

Reaction notes

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