1,3-Oxazolidine → 3-(5-tert-Butyloxazol-4-yl)-2-hydroxyacrylic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of Ethyl 5-(tert-butyl)oxazole-4-carboxylate 2 (20 g, 101 mmol) in anhydrous THF (250 mL) was added LiAl (3.84 g, 101 mmol, Kanto Chemical, Tokyo, Japan, Cat. No. 24115-35) portionwise under argon atmosphere at −60° C., and the bath temperature was gradually increased up to −40° C. with stirring for 2 h. (In case that the temperature was more than −40° C., the reduction of the oxazole ring (oxazolidine formation) predominantly proceeded). After the reaction mixture was quenched with saturated NH4Cl aq (50 ml) at −60° C. (Please avoid rapid elevation of temperature. Some impurity increased.), AcOEt (250 ml) was-added and stirred for a few minutes, and the resulting precipitate was removed by celite filtration (Celite-535, Nacalai Tesque, Kyoto, Japan, Cat. No. 07509-05). The filtrate was washed with water (×2), 10% citric acid (×3, a byproduct, oxazolidine, can be removed by this separation) and saturated NaCl (×3), dried over anhydrous Na2SO4, and concentrated in vacuo to give an oil of corresponding oxazole alcohol 3 (10.6 g, 67%). Rf 0.50 (CHCl3:MeOH=10:0.5), 1H NMR (300 MHz CDCl3) δ 7.71 (s, 1H), 4.66 (s, 2H), 1.36 (s, 9H); HRMS(EI): m/z 155.0852 (M+) (Calcd for C8H13NO2: 155.0854). This oil was used to the next oxidation without further purification.

Provenance & Evidence