Hydrochloric Acid → Ethyl 3-(2-fluoro-4-methoxyphenyl)-3-oxopropanoate

HRID 336826Notes

Reaction equation

HRID 336826 reaction equation
[CH2:1]([O:3][C:4](=[O:9])[CH2:5][C:6]([O-:8])=O)[CH3:2].[K+].[Cl-].[Mg+2].[Cl-].[F:14][C:15]1[CH:23]=[C:22]([O:24][CH3:25])[CH:21]=[CH:20][C:16]=1C(Cl)=O.Cl>C(#N)C.C(N(CC)CC)C>[F:14][C:15]1[CH:23]=[C:22]([O:24][CH3:25])[CH:21]=[CH:20][C:16]=1[C:6](=[O:8])[CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:9]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 3446434Potassium ethyl malonateHCID 5360315Magnesium ChlorideHCID 144847142-Fluoro-4-methoxybenzoyl chloride

Product 1

HCID 53811014Ethyl 3-(2-fluoro-4-methoxyphenyl)-3-oxopropanoateYield 78.4%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 8471TriethylamineSolvent2×

Procedure

To a solution of 12.34 g (72.5 mmol) of potassium 3-ethoxy-3-oxopropanoate in suspension in 150 ml anhydrous acetonitrile are added at −0° C. under argon 10.11 ml (72.5 mmol) of triethylamine and 8.28 g (87 mmol) of magnesium (II) chloride. The reaction mixture is stirred for 5 h at room temperature, then at 0° C. a solution of 5.47 g (29 mmol) of 2-fluoro-4-methoxybenzoyl chloride dissolved in 30 ml of acetonitrile is added as well as 4.45 ml (31.9 mmol) of triethylamine. The reaction mixture is stirred for 18 h at room temperature then a 1M hydrochloric acid solution is added until the suspension disappears. The product is extracted several times with ethyl acetate. The organic phases are combined, dried over magnesium sulfate, and concentrated. The residue is purified by chromatography on silica (cyclohexane/ethyl acetate eluent: 85:15) to yield 5.46 g (78%) of ethyl 3-(2-fluoro-4-methoxyphenyl)-3-oxopropanoate in the form of a yellow oil which crystallizes over time.

Workup

  1. stirringThe reaction mixture is stirred for 18 h at room temperature
  2. extractionThe product is extracted several times with ethyl acetate
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. customThe residue is purified by chromatography on silica (cyclohexane/ethyl acetate eluent: 85:15)

Sources & evidence

ORD record
ord-dab8b5d7342c4c1598ca25d4cb23ee34
Source dataset
uspto-grants-2014_11
Patent number
US08889711B2

Reaction notes

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