Sodium hydride → 2-(4-fluorobenzyl)-3-oxopentanoic Acid Methyl Ester

HRID 2266548Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:9])[CH2:4][C:5](=[O:8])[CH2:6][CH3:7].[H-].[Na+].Br[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=1>CN(C)C=O.O1CCCC1>[CH3:1][O:2][C:3](=[O:9])[CH:4]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=1)[C:5](=[O:8])[CH2:6][CH3:7]

Participants

Conditions

Temperature: 0 °C

Procedure

3-Oxopentanoic acid methyl ester (7.5 g) was added to a stirred suspension of sodium hydride (60% in oil, 4.6 g) in N,N-dimethylformamide (20 mL) and tetrahydrofuran (80 mL) at 0° C. and the resulting mixture stirred at 0° C. for 30 minutes. A solution of 1-bromomethyl-4-fluorobenzene (7.0 mL) in tetrahydrofuran was added and the resulting mixture warmed to room temperature and then stirred at this temperature for 17 hours. The mixture was partitioned between ethyl acetate and water and the aqueous phase extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate and the solvent removed under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (19:1 by volume) to afford title compound, 1.0 g.

Workup

temperaturethe resulting mixture warmed to room temperature
stirringstirred at this temperature for 17 hours
customThe mixture was partitioned between ethyl acetate and water
extractionthe aqueous phase extracted with ethyl acetate
dry with materialThe combined organic phases were dried over sodium sulfate
customthe solvent removed under reduced pressure
customThe residue was purified by column chromatography on silica gel
washeluting with a mixture of cyclohexane and ethyl acetate (19:1 by volume)

Sources & evidence

ORD record: ord-a507e242d645476f96525c741de41f09
Source dataset: uspto-grants-2010_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07858640B2

Reaction notes

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