Methyl 2-(4-((3-chloro-5-(trifluoromethyl)-2-pyridinyl)oxy)phenoxy)propanoate synthesis

Yield:-

Reaction Conditions:

with tetrabutylammomium bromide in water

Steps:

1 Preparation of Methyl 2-(4-((3-Chloro-5-trifluoromethyl-2-pyridinyl)oxy)-phenoxy)propionate STR4
Example 1 Preparation of Methyl 2-(4-((3-Chloro-5-trifluoromethyl-2-pyridinyl)oxy)-phenoxy)propionate STR4 A 500 milliliter (mL) round-bottom flask was equipped with a mechanical paddle stirrer, an infrared heater connected to a thermocouple temperature controller and a drying tube. Methyl 2-(4-hydroxyphenoxy)propionate (103 grams (g): 0.5 moles) was introduced into the flask and heating was initiated to melt the solid. Stirring was begun and powdered anhydrous Na₂ CO₃ (74.2 g: 0.70 moles) was added. After 5 minutes (min), the temperature was about 80° C. and the evolution of gas was proceeding. Tetra-n-butylammonium bromide (4.8 g: 0.015 moles) was added, followed by 100 g (0.5 moles) of 2-fluoro-3-chloro-5-trifluoromethylpyridine. After 70 min at 80° C, the temperature was raised to 90° C. for an additional 230 min. The reaction mixture was allowed to cool and 750 mL of water and 500 mL of CH₂ Cl₂ were added. After mixing, the layers were separated. The aqueous layer was extracted with 50 mL of CH₂ Cl₂ and the combined organic layers were washed with 50 mL of water. The solvent was evaporated under reduced pressure to give 200.4 g of viscous oil. After 3 days, the oil began to crystallize. The product was recrystallized from methanol and dried to give 148.3 g of white solid, mp 55.5°-56.5° C.

References:

DowElanco US5049675, 1991, A

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