Sodium hydride → Ethyl phenylmethyl (3-fluoro-4-nitrophenyl)propanedioate

HRID 913174Notes

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:25]=[C:24](F)[CH:23]=[CH:22][C:21]=1[N+:27]([O-:29])=[O:28]>CN(C=O)C>[F:19][C:20]1[CH:25]=[C:24]([CH:4]([C:3]([O:11][CH2:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)=[O:10])[C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH:23]=[CH:22][C:21]=1[N+:27]([O-:29])=[O:28]

Participants

Conditions

Temperature: 10 °C

Procedure

Sodium hydride (17.8 g, 445 mmol) was added portionwise to a solution of benzyl ethyl malonate (98.9, 445 mmol) in dry DMF (280 ml) and stirred for 10 minutes. Cooled to 10° C. over 30 minutes. 2,4-difluoro-1-nitrobenzene (48.9 ml, 445 mmol) was added and stirred at room temperature for 16 hours. The reaction mixture was quenched with 2N hydrochloric acid (150 ml) to pH 3-4 then extracted ×2 with ether. The combined organics washed with 2× water and brine, dried over magnesium sulphate and evaporated to a yellow oil. Purified by chromatography on silica gel eluting with 5% ethyl acetate in hexane to give the title compound as a yellow oil (11.66, 32.3 mmol). LC/MS: Rt=3.39, [MH]− 360.

Workup

stirringstirred at room temperature for 16 hours
customThe reaction mixture was quenched with 2N hydrochloric acid (150 ml) to pH 3-4
extractionthen extracted ×2 with ether
washThe combined organics washed with 2× water and brine
dry with materialdried over magnesium sulphate
customevaporated to a yellow oil
customPurified by chromatography on silica gel eluting with 5% ethyl acetate in hexane

Sources & evidence

ORD record: ord-5ee2a5c5f2444ffaa482671e9e5c519e
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08026270B2

Reaction notes

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