Sodium hydride → Ethyl phenylmethyl (2-fluoro-4-nitrophenyl)propanedioate

HRID 1879107Notes

Reaction equation

[H-].[Na+].[C:3]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)(=[O:10])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].[F:19][C:20]1[CH:21]=[C:22]([N+:27]([O-:29])=[O:28])[CH:23]=[CH:24][C:25]=1F>CN(C=O)C>[F:19][C:20]1[CH:21]=[C:22]([N+:27]([O-:29])=[O:28])[CH:23]=[CH:24][C:25]=1[CH:4]([C:3]([O:11][CH2:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)=[O:10])[C:5]([O:7][CH2:8][CH3:9])=[O:6]

Participants

Conditions

Temperature: 100 °C

Procedure

Sodium hydride (504 mg, 12.6 mmol) was added portionwise to an ice bath chilled solution of benzyl ethyl malonate (2.9 g, 12.6 mmol) in dry DMF (20 ml) and stirred for 10 minutes. At room temperature 3,4-difluoronitrobenzene (2 g, 12.6 mmol) was added and stirred under argon. Heated at 100° C. for 20 hours. The reaction mixture was cooled and partitioned between 2N Hydrochloric acid (75 ml) and ethyl acetate (75 ml). The aqueous layer was extracted with ethyl acetate (2×75 ml) and the combined organics were evaporated to a yellow oil. Purified by chromatography on silica gel eluting with ethyl acetate/hexane (1:4) to give the title compound as a yellow oil (3.86 g, 10.6 mmol). LC/MS: Rt=3.40, [MH]+ 362

Workup

stirringstirred under argon
temperatureThe reaction mixture was cooled
custompartitioned between 2N Hydrochloric acid (75 ml) and ethyl acetate (75 ml)
extractionThe aqueous layer was extracted with ethyl acetate (2×75 ml)
customthe combined organics were evaporated to a yellow oil
customPurified by chromatography on silica gel eluting with ethyl acetate/hexane (1:4)

Sources & evidence

ORD record: ord-c2774d81e9044045aa40c41dcecdccc4
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08314147B2

Reaction notes

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