Hydrochloric Acid → Imiglitazar

Participants

Reaction Steps

Under a nitrogen atmosphere, sodium hydride (60%; oily; 3.00 g) was added to a solution of methyl (E)-4-hydroxyimino-4-phenylbutyrate (15.5 g) and 4-(4-chloromethylphenoxymethyl)-5-methyl-2-phenyloxazole (23.5 g) in N,N-dimethylformamide (100 ml) at 0° C. and the mixture was stirred for 2 hours. This was neutralized with 1N hydrochloric acid, aqueous solution of sodium bicarbonate was added thereto and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous solution of sodium chloride, dried (over MgSO4) and concentrated. The residue was subjected to a silica gel column chromatography and an oily product was obtained from an eluate with ethyl acetate-hexane (1:3, volume ratio). This was dissolved in tetrahydrofuran (100 ml)-methanol (50 ml), a 2N aqueous solution of sodium hydroxide (50 ml) was added thereto and the mixture was stirred at room temperature for 2 hours. The reaction mixture was neutralized with 1N hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous solution of sodium chloride dried (over MgSO4) and concentrated. The resulting crystals were recrystallized from ethyl acetate-hexane to give colorless crystals of (E)-4-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyloxyimino]-4-phenylbutyric acid (24.5 g; yield: 86%). Melting point: 126-127° C. A part (500 mg) of the crystals was dissolved in ethanol (5 ml) with heating and cooled at 0° C. The precipitating crystals were collected to give crystals (466 mg) showing a powder X-ray crystal diffraction pattern as given in FIG. 2. Melting point: 137-138° C.

Provenance & Evidence