Hydroxyamine hydrochloride → tert-butyl 1-(3-chloro-4-(N'-hydroxycarbamimidoyl)benzyl)azetidine-3-carboxylate

Participants

Reaction Steps

A solution of tert-butyl 1-(3-chloro-4-cyanobenzyl)azetidine-3-carboxylate (0.133 g, 0.434 mmol) in isopropanol (1.2 mL) with hydroxylamine hydrochloride (0.060 g, 0.868 mmol) and sodium bicarbonate (0.146 g, 1.74 mmol) was stirred at 90° C. for 6.5 hrs. HPLC and LCMS indicated the reaction was only 33% complete after 20 minutes. Additional hydroxylamine hydrochloride (0.060 g) and sodium bicarbonate (0.146 g) were added and heating was continued for 5 hrs. The isopropanol was removed under reduced pressure, and the reaction mixture was diluted with ethyl acetate and washed with water (2×), washed with brine, and dried over anhydrous sodium sulfate. Concentration under reduced pressure afforded tert-butyl 1-(3-chloro-4-(N′-hydroxycarbamimidoyl)benzyl)azetidine-3-carboxylate (142 mg) of a tan viscous taffy. The compound had an HPLC ret. time=0.795 min.−Column. PHENOMENEX® S5 4.6×30 mm (2 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. MS M+1=340.11.

Provenance & Evidence