Diethyl Malonate → Diethyl 2-(3-(2-fluoro-4-biphenylyl)-2-oxobutyl)malonate

HRID 256777Notes

Reaction equation

HRID 256777 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].Cl[CH2:15][C:16](=[O:32])[CH:17]([C:19]1[CH:24]=[CH:23][C:22]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[C:21]([F:31])[CH:20]=1)[CH3:18]>CN(C)C=O>[F:31][C:21]1[CH:20]=[C:19]([CH:17]([CH3:18])[C:16](=[O:32])[CH2:15][CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[C:3]([O:11][CH2:12][CH3:13])=[O:10])[CH:24]=[CH:23][C:22]=1[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

5

Reactant 3

HCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 156760091-Chloro-3-(2-fluoro-4-biphenylyl)-2-butanone

Product 1

HCID 19785556Diethyl 2-(3-(2-fluoro-4-biphenylyl)-2-oxobutyl)malonateYield 62%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of sodium hydride (1.88 g as 60% in oil, 47.0 mmoles) which was washed with hexane to remove mineral oil and dried, in dimethylformamide (DMF, 23 ml) was added dropwise a solution of diethyl malonate (7.52 g, 47.0 mmoles) in DMF (5 ml) at 0° C. under the stream of nitrogen gas. After elevating the temperature to 50° C., a solution of 1-chloro-3-(2-fluoro-4-biphenylyl)butan-2-one (10.0 g, 36.1 mmoles) in DMF (40 ml) was added dropwise, and the resulting mixture was stirred at the same temperature for 2 hours. The reaction mixture was poured into ice water and extracted with diethyl ether. The organic layer was washed with 1M hydrochloric acid, dried over sodium sulfate and concentrated under reduced pressure. Purification of the residue by medium pressure silica gel column chromatography gave the desired diethyl 2-(3-(2-fluoro-4-biphenylyl)-2-oxobutyl)malonate (8.98 g, 22.4 mmoles, yield 62%) as a light yellow oil.

Workup

  1. washwas washed with hexane
  2. customto remove mineral oil
  3. dry with materialdried, in dimethylformamide (DMF, 23 ml)
  4. customto 50° C.
  5. extractionextracted with diethyl ether
  6. washThe organic layer was washed with 1M hydrochloric acid
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customPurification of the residue by medium pressure silica gel column chromatography

Sources & evidence

ORD record
ord-3f9b270d60de4f5090a98ca469ea611f
Source dataset
uspto-grants-1993_11
Patent number
US05258396

Reaction notes

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