Dimethyl malonate → HCID 10322194, compound

HRID 275479

Reaction equation

HRID 275479 reaction equation
[C:1]([O:8][CH3:9])(=[O:7])[CH2:2][C:3]([O:5][CH3:6])=[O:4].[H-].[Na+].Br[CH2:13][C:14]([C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=1)=[O:15].Br[CH2:24][C:25]([C:27]1[CH:32]=[CH:31][C:30]([S:33]([CH3:36])(=[O:35])=[O:34])=[CH:29][CH:28]=1)=[O:26]>CN(C=O)C>[CH3:6][O:5][C:3](=[O:4])[C:2]([CH2:13][C:14]([C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=1)=[O:15])([CH2:24][C:25]([C:27]1[CH:28]=[CH:29][C:30]([S:33]([CH3:36])(=[O:35])=[O:34])=[CH:31][CH:32]=1)=[O:26])[C:1]([O:8][CH3:9])=[O:7]

Participants

6

Reactant 4

HCID 7943Dimethyl malonateHCID 24758Sodium hydride2×HCID 967492-Bromo-1-(4-fluorophenyl)ethan-1-oneHCID 7358232-Bromo-4'-(methylsulfonyl)acetophenone

Product 1

HCID 10322194HCID 10322194, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 7.18 mL (63 mmol) of dimethyl malonate in 160 mL of DMF at 0° C. under an atmosphere of nitrogen was added 3.0 g (75 mmol) of sodium hydride (60% suspension in oil). The reaction was stirred at ambient temperature for 15 minutes (or until the gas evolution has ceased), cooled to -20° C., and treated with 15 g (69 mmol) of 2-bromo-4'-fluoroacetophenone (Aldrich) in one portion. The mixture was stirred at ambient temperature for 1 hour and then cooled to 0° C.; another 75 mmol of sodium hydride was added and the resulting mixture stirred at ambient temperature for 15 minutes (or until the gas evolution has ceased). The reaction was recooled to -20° C. and treated with 19.1 g (69 mmol) of 2-bromo-4'-(methylsulfonyl)acetophenone (prepared in Step 3). The reaction was stirred at room temperature for 2 hours and concentrated in vacuo. The residue was partitioned between water and ethyl acetate; the ethyl acetate phase was dried (MgSO4) and reconcentrated in vacuo. The residue was chromatographed on silica gel to give 13.8 g (51%) of dimethyl2-[2-(4-fluorophenyl)-2-oxoethyl]-2-[2-[4-(methylsulfonyl)phenyl]-2-oxoethyl]propanedioate as an oil: NMR (CDCl3) δ 3.06 (s, 3H), 3.76 (s, 6H), 4.03 (s, 2H), 4.08 (s, 2H), 7.13 (t, J=8.6 Hz, 2H), 7.97-8.05[m with d at 8.03 (J=8.7 Hz), 4H], 8.14 (d, J=8.5 Hz, 2H).

Workup

  1. temperaturecooled to -20° C.
  2. stirringThe mixture was stirred at ambient temperature for 1 hour
  3. temperaturecooled to 0° C.
  4. stirringthe resulting mixture stirred at ambient temperature for 15 minutes (or until the gas evolution
  5. customwas recooled to -20° C.
  6. stirringThe reaction was stirred at room temperature for 2 hours
  7. concentrationconcentrated in vacuo
  8. customThe residue was partitioned between water and ethyl acetate
  9. dry with materialthe ethyl acetate phase was dried (MgSO4)
  10. customThe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-b74f8b3bdbaa492bae283f54b6f4cad1
Source dataset
uspto-grants-1995_02
Patent number
US05393790

Linked notes

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