Water → HCID 57659600, compound

HRID 1172596Notes

Reaction equation

HRID 1172596 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].[F:14][C:15]1[C:22]([CH3:23])=[CH:21][CH:20]=[CH:19][C:16]=1[CH2:17]Br.O>C(COC)OC>[CH2:12]([O:11][C:3](=[O:10])[CH:4]([CH2:17][C:16]1[CH:19]=[CH:20][CH:21]=[C:22]([CH3:23])[C:15]=1[F:14])[C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH3:13]

Participants

6

Reactant 4

HCID 962WaterHCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 519062Benzene, 1-(bromomethyl)-2-fluoro-3-methyl-

Product 1

HCID 57659600HCID 57659600, compoundYield 70.1%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent3×

Procedure

To a suspension of sodium hydride (215 mg, 4.92 mmol) in dimethoxyethane (3 ml) was added dropwise a solution of diethyl malonate (868 mg, 5.42 mmol) in dimethoxyethane (2 ml) in an inert atmosphere at rt. Stirring was continued for 1 h followed by the addition of a solution of 2-fluoro-3-methyl-benzylbromide (1 g, 4.92 mmol) in dimethoxyethane (15 ml). The reaction mixture was refluxed for 90 minutes, cooled again to rt and water (5 ml) was carefully added. The diemthoxyethane was removed under reduced pressure, DCM (100 ml) was added and the organic layer was washed with water (100 ml), dried over magenisum sulfate, filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography (silicagel, DCM/heptane=4/1) to give 973 mg (70%) of 2-(2-fluoro-3-methyl-benzyl)-malonic acid diethyl ester. LC-MS: tR=1.03 min; [M+H]+=283.22.

Workup

  1. temperatureThe reaction mixture was refluxed for 90 minutes
  2. customThe diemthoxyethane was removed under reduced pressure, DCM (100 ml)
  3. additionwas added
  4. washthe organic layer was washed with water (100 ml)
  5. dry with materialdried over magenisum sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by flash chromatography (silicagel, DCM/heptane=4/1)

Sources & evidence

ORD record
ord-d988d5890f584c81954827eea1977e9c
Source dataset
uspto-grants-2010_11
Patent number
US07834028B2

Reaction notes

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