Hydrochloric Acid → 1-(2-Fluoro-4-methoxyphenyl)-2-(methylsulfonyl)ethanone

HRID 336827Notes

Reaction equation

HRID 336827 reaction equation
[CH3:1][S:2]([CH3:5])(=[O:4])=[O:3].C[Li].[F:8][C:9]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:10]=1[C:11](Cl)=[O:12].Cl>O1CCCC1>[F:8][C:9]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:10]=1[C:11](=[O:12])[CH2:1][S:2]([CH3:5])(=[O:4])=[O:3]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6213Dimethyl SulfoneHCID 144847142-Fluoro-4-methoxybenzoyl chlorideHCID 178418348HCID 178418348, compound

Product 1

HCID 640182411-(2-Fluoro-4-methoxyphenyl)-2-(methylsulfonyl)ethanoneYield 46%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4.15 g (44.07 mmol) of dimethylsulfone in 140 ml of anhydrous tetrahydrofuran are added dropwise at −10° C. under argon 24 ml of methyllithium solution (1.6M in diethyl ether, 38.2 mmol). The reaction mixture is stirred for 15 min at room temperature, the reaction mixture is then cooled to −60° C. A solution of 5.54 g (29.38 mmol) of 2-fluoro-4-methoxybenzoyl chloride dissolved in 60 ml of tetrahydrofuran is then added dropwise to the reaction mixture. This mixture is stirred for 4 h at between −60° C. and 0° C., then a 1M hydrochloric acid solution is added. The product is extracted several times with ethyl acetate. The organic phases are combined, dried over magnesium sulfate and concentrated. The residue is triturated in minimum methanol and the solid is filtered to yield 3.33 g (46%) of 1-(2-fluoro-4-methoxyphenyl)-2-(methylsulfonyl)ethanone in the form of a white solid.

Workup

  1. temperaturethe reaction mixture is then cooled to −60° C
  2. additionis then added dropwise to the reaction mixture
  3. stirringThis mixture is stirred for 4 h at between −60° C. and 0° C.
  4. extractionThe product is extracted several times with ethyl acetate
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. customThe residue is triturated in minimum methanol
  8. filtrationthe solid is filtered

Sources & evidence

ORD record
ord-e21e3085a0774f6ea1f6a21382f2eb24
Source dataset
uspto-grants-2014_11
Patent number
US08889711B2

Reaction notes

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