Methanol → 2-{3-[2-(4-Fluorophenyl)oxazol-4-ylmethoxy]phenoxymethyl}-6-methylbenzoic acid

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Reaction Steps

18.6 g of 30% strength solution of sodium methoxide in methanol (104 mmol) are added to 15.9 g (51.6 mmol) of 2-(3-hydroxyphenoxymethyl)-6-methyl-benzoic acid (hemisolvate with N-methylpyrrolidone) in 70 ml of N-methylpyrrolidone while stirring at room temperature. After five minutes, 10.0 g (47.3 mmol) of 4-chloromethyl-2-(4-fluorophenyl)oxazole are added, and the mixture is stirred at room temperature for 23 h and finally heated at 50° C. for one hour. 500 ml of 19% strength sodium chloride solution are added to the reaction solution, and the resulting mixture is extracted twice with 225 ml of ethyl acetate. The combined ethyl acetate phases are extracted three times with 225 ml of water, and the combined aqueous phases are acidified to pH=3 with 2 M hydrochloric acid. The resulting crystals are filtered off with suction and washed with water. The product is purified further by crystallization from isopropanol. 2-{3-[2-(4-Fluorophenyl)oxazol-4-ylmethoxy]phenoxymethyl}-6-methylbenzoic acid is obtained as colorless crystals in a yield of 58.3%, melting point 168-173° C.

Provenance & Evidence