Methyl chlorodifluoroacetate → 4-Chloro-2-trifluoromethyl-6-methyl-benzoic acid methyl ester

HRID 2427676Notes

Reaction equation

HRID 2427676 reaction equation
[F-:1].[K+].[CH3:3][O:4][C:5](=[O:15])[C:6]1[C:11]([CH3:12])=[CH:10][C:9]([Cl:13])=[CH:8][C:7]=1I.COC(=O)[C:19](Cl)([F:21])[F:20]>CN(C=O)C.[Cu]I>[CH3:3][O:4][C:5](=[O:15])[C:6]1[C:11]([CH3:12])=[CH:10][C:9]([Cl:13])=[CH:8][C:7]=1[C:19]([F:21])([F:1])[F:20]

Participants

6

Reactant 3

HCID 73935Methyl chlorodifluoroacetateHCID 522689Potassium FluorideHCID 67192903Methyl 4-chloro-2-iodo-6-methylbenzoate

Product 1

HCID 579494324-Chloro-2-trifluoromethyl-6-methyl-benzoic acid methyl esterYield 67.4%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

CuI (1.9 g, 10 mmol) and potassium fluoride (0.58 g, 10 mmol) were added under an N2 atmosphere to a solution of 4-chloro-2-iodo-6-methyl-benzoic acid methyl ester (2.9 g, 9.4 mmol) and chloro-difluoro-acetic acid methyl ester (1.2 mL, 11 mmol) in DMF (25 mL). The mixture was stirred at 140° C. for 18 h. The reaction was cooled and the solvent evaporated. Silica gel column chromatography using 10% ethyl acetate in hexane afforded 4-chloro-2-trifluoromethyl-6-methyl-benzoic acid methyl ester (1.6 g, 67%). GC-MS: m/z 252 (M−1)+, 221 (M−31)+.

Workup

  1. temperatureThe reaction was cooled
  2. customthe solvent evaporated

Sources & evidence

ORD record
ord-14fd7c9cdfb9490286d98954739ab7a0
Source dataset
uspto-grants-2011_06
Patent number
US07968570B2

Reaction notes

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