1-Hydroxybenzotriazole → Tert-butyl 1-(4-(5-(4-isobutyl-5-phenylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate

Participants

Reaction Steps

A mixture of 4-isobutyl-5-phenylisoxazole-3-carboxylic acid, lithium salt (0.119 g, 0.472 mmol), (Z)-tert-butyl 1-(4-(N′-hydroxycarbamimidoyl)benzyl)azetidine-3-carboxylate (Int.1, 0.144 g, 0.472 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (0.090 g, 0.472 mmol), and HOBt (0.072 g, 0.472 mmol) in N,N-dimethylformamide (3.6 mL) was stirred at room temperature for 15 min and then heated at 60° C. overnight. The reaction mixture was diluted with ethyl acetate, washed with a saturated aqueous solution of sodium bicarbonate (2×), washed with a 10% aqueous solution of lithium chloride (2×), and dried over anhydrous sodium sulfate. The product mixture was concentrated under reduced pressure. The residue was purified by flash silica gel chromatography using a 1% mixture of methanol in dichloromethane to give tert-butyl 1-(4-(5-(4-isobutyl-5-phenylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate (0.179 g) as a pale yellow solid. The ester intermediate was 98% pure by HPLC with a ret. time=3.27 min.−Column: CHROMOLITH® SpeedROD 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. LC/MS M+1=515.4.

Provenance & Evidence