Methanol → Benzoic acid, 5-chloro-2-hydroxy-, methyl ester

Participants

Reaction Steps

5-Chlorosalicylic acid was treated with one equivalent of 18M sulfuric acid in refluxing methanol for 20 h to give methyl 5-chlorosalicylate. After recrystallization from isopropyl ether the salicylate was treated with the sodium salt of N-chloro-p-toluylsulfonamide in dimethylformamide in the presence of an excess of sodium iodide to give methyl 5-chloro-3-iodosalicylate. Treatment with 2-bromoethanol in refluxing acetone in the presence of an excess of potassium carbonate for 10 h gave methyl 5-chloro-3-iodo-2-(2-hydroxyethoxy)benzoate which was subsequently hydrolyzed in ethanol containing 3N NaOH to give 5-chloro-3-iodo-2-(2-hydroxyethoxy)benzoic acid. The acid was treated with 1,1-carbonyldiimidazole in DMF for 1 h, the resulting imidazole amide condensed with (S)-3-aminoquinuclidine. The resulting substituted chlorobenzamide was purified by acid-base extractions and the hydroxy group was protected by a toluenesulfonyl group. The tosylate can be reacted with 50 mCi of hydro[18F]fluoric acid, prepared from H2 [18O]O in an 11 MeV cyclotron and K2CO3 -kryptofix[222] in acetonitrile for 20 min at 120° C. and purified by HPLC, to produce the radiochemical pure product of [18F]-18.

Provenance & Evidence