M-Cresol → 2-Methyl-2-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-2-m-tolyloxymethyl-phenoxy}-propionic acid

Participants

Reaction Conditions

Reaction Steps

General procedure for the parallel synthesis of analogs using the DynaVac Carousel apparatus: A 50 mL glass tube with screw cap and nitrogen inlet was charged with 2-{2-bromomethyl-4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenoxy}-2-methyl-propionic acid ethyl ester (0.040 g, 0.080 mmol), m-cresol (0.012 mL, 0.12 mmol), absolute ethanol (1 mL), and then potassium carbonate (0.022 g, 0.16 mmol; 325 mesh). The mixture was heated to 80° C. for 4 h. MS analysis of the reaction indicated that 2-methyl-2-{4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]-2-m-tolyloxymethylphenoxy}-propionic acid ethyl ester: MS (ES) m/e 530 (M+1) had formed. The reaction mixture was treated with 2N NaOH (0.4 mL), heated at 55° C. for 3 h, cooled, and concentrated. The residue was treated with 5N HCl (0.75 mL) and CH2Cl2 (1 mL) and was poured onto a 3-mL ChemElute cartridge to remove the aqueous layer. The cartridge was washed with CH2Cl2, and the solvent was removed in vacuo. The crude residue was purified by mass-directed reverse phase HPLC to provide the title compound (0.032 g, 38%). MS (ES) m/e 502 (M+1).

Provenance & Evidence