The general procedure for the synthesis of isoxazolidine hydrochloride from 1,3-dichloropropane was as follows: first, 1,3-dichloropropane (1.6 mL, 15 mmol, 1.2 eq.) and DBU (1,8-diazabicyclo[5.4.0]undec-7-ene; 1.8 mL, 12 mmol, 1.0 eq.) were sequentially added to a stirring solution of 2-hydroxyisoindoline-1,3 -dione (N-hydroxyphthalimide; 2.0 g, 12 mmol, 1.0 eq.) in a solution of DMF (30 mL) at a reaction temperature of 23 °C. The reaction mixture was heated to 50 °C and stirred continuously for 18 hours. Upon completion of the reaction, the resulting colorless solution was diluted with 1 M aqueous HCl (300 mL) and extracted with ether (Et2O; 2 x 100 mL). The organic layers were combined, dried with anhydrous magnesium sulfate (MgSO4), gravity filtered and concentrated by rotary evaporation to give a colorless oil (1.5 g). The oil was dissolved in ethanol (EtOH; 15 mL), hydrazine hydrate (300 μL, 11 mmol, 1.0 eq.) was added, and the light yellow suspension was stirred at 23 °C for 4 h. The reaction mixture was filtered under vacuum. The reaction mixture was filtered under vacuum and the filtrate was concentrated by rotary evaporation to give a light yellow powdery product (530 mg, 77% yield). The structure of the product was confirmed by 1H NMR (300 MHz, DMSO-d6): δ 5.34 (broad single peak, 2H), 4.07 (triple peak, J = 7 Hz, 2H), 3.37 (triple peak, J = 7 Hz, 2H), 2.30 (quintuple peak, J = 7 Hz, 2H).
