Methanol → methyl 4-chloro-3-fluorobenzoate

HRID 1846972Notes

Reaction equation

HRID 1846972 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[F:11].S(Cl)(Cl)=O.[CH3:16]O>>[CH3:16][O:7][C:6](=[O:8])[C:5]1[CH:9]=[CH:10][C:2]([Cl:1])=[C:3]([F:11])[CH:4]=1

Participants

4

Reactant 3

HCID 887MethanolHCID 24386Thionyl ChlorideHCID 27365364-Chloro-3-fluorobenzoic acid

Product 1

HCID 2780856methyl 4-chloro-3-fluorobenzoate

Procedure

A solution of 4-chloro-3-fluoro benzoic acid (450.0 g, 2.586 mol, Fluororochem, Derbyshire, UK) in methanol (4.5 L) was cooled to 0° C. and thionyl chloride (450.0 mL) was added over 30 minutes. The reaction mixture was stirred for 12 hours at ambient temperature. The reaction was monitored by TLC. Upon completion, the solvent was removed under reduced pressure and the residue was quenched with 1.0 M sodium bicarbonate solution (500 mL). The aqueous layer was extracted with dichloromethane (2×5.0 L). The combined organic layer was washed with brine (2.5 L), dried over anhydrous sodium sulfate and concentrated under reduced pressure afforded the title compound as light brown solid. The crude compound was used in the next step without further purification.

Workup

  1. customUpon completion, the solvent was removed under reduced pressure
  2. customthe residue was quenched with 1.0 M sodium bicarbonate solution (500 mL)
  3. extractionThe aqueous layer was extracted with dichloromethane (2×5.0 L)
  4. washThe combined organic layer was washed with brine (2.5 L)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-2e24bd45f6d5472fa78149e606756173
Source dataset
uspto-grants-2015_02
Patent number
US08952036B2

Reaction notes

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