Diethyl Malonate → 1,3-Diethyl 2-(3,5-difluoro-2-pyridinyl)propanedioate

HRID 82285Notes

Reaction equation

F[C:2]1[C:7]([F:8])=[CH:6][C:5]([F:9])=[CH:4][N:3]=1.[C:10]([O:18][CH2:19][CH3:20])(=[O:17])[CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13].C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O.C(OCC)(=O)C>[CH2:15]([O:14][C:12](=[O:13])[CH:11]([C:2]1[C:7]([F:8])=[CH:6][C:5]([F:9])=[CH:4][N:3]=1)[C:10]([O:18][CH2:19][CH3:20])=[O:17])[CH3:16]

Participants

Conditions

Temperature: 110 °C

Procedure

To a stirred solution of 2,3,5-trifluoro-pyridine (2 g, 15.02 mmol) in dimethyl sulfoxide (20 mL) was added diethyl malonate (4.60 g, 28.72 mmol). Then cesium carbonate (9.35 g, 28.72 mmol) was added and the reaction mixture was heated to 110° C. for 16 hours. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (100 mL). The organic layer was washed with water (2×25 mL), brine (25 mL), dried over sodium sulphate and evaporated in vacuo to afford the title compound as oil in 85% yield, 3.5 g.

Workup

temperatureThe reaction mixture was cooled to room temperature
washThe organic layer was washed with water (2×25 mL), brine (25 mL)
dry with materialdried over sodium sulphate
customevaporated in vacuo

Sources & evidence

ORD record: ord-d7a2bddfc36c49a9939cb41f30b06704
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846698B2

Reaction notes

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