3.10.2 Synthesis of ethyl 5-(tert-butyl)-1,2,4-oxadiazole-3-carboxylate (949-4)
Under stirring conditions, ethyl 2-hydroxyamino-2-iminoacetate (5.0 g, 37.8 mmol) was dissolved in DMF (60 mL), and pivalic acid (3.86 g, 37.8 mmol), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDCI, 7.97 g, 41.58 mmol), 1-hydroxybenzo triazole (HOBt, 6.12 g, 45.3 mmol) and N,N-diisopropylethylamine (DIPEA, 19.7 mL, 113.4 mmol). The reaction mixture was stirred at room temperature overnight and then heated to 100 °C for 1 hour. After cooling to room temperature, the extract was partitioned with ethyl acetate (EA) and water. The organic layer was separated and the aqueous layer was back-extracted with ethyl acetate (3×). The organic layers were combined, washed with saturated brine and dried over anhydrous sodium sulfate. After concentration under reduced pressure, the residue was purified by fast column chromatography (silica gel, petroleum ether/ethyl acetate = 10:90 to 90:10) to afford the target product, ethyl 5-(tert-butyl)-1,2,4-oxadiazole-3-carboxylate (949-4) (1.8 g, 24%), as a yellow solid.LC-MS: ESI m/z (M+1) = 199.36.
