1522-92-5

70-55-3

13573-28-9

General procedure for the synthesis of 6-(p-toluenesulfonyl)-2-oxo-6-azaspiro[3.3]heptane by the reaction of 2,2-bis(bromomethyl)-3-bromo-1-propanol with p-toluenesulfonamide: 1. prepare a reaction solution by dissolving KOH (179 g, 3.2 mol) and p-toluenesulfonamide (205 g, 1.2 mol) in 1500 mL of ethanol. 2. 2,2-bis(bromomethyl)-3-bromo-1-propanol (324 g, 1.0 mol) was slowly added to the above solution at room temperature. 3. The reaction mixture was heated to reflux and kept reacting for 90 hours. 4. Upon completion of the reaction, the solvent was removed by evaporation. 5. 2000 mL of 1M KOH solution was added to the residue to form a white suspension, which continued to be stirred at room temperature for 2 hours. 6. The reaction mixture was filtered and the white filter cake was washed repeatedly with water until the wash water was neutral. 7. The filter cake was dried under high vacuum to afford the target product N-toluenesulfonyl-2-oxa-6-azaspiro[3.3]heptane (5,192 g, 76% yield) as a white solid. Product characterization data: 1H NMR (400 MHz, CDCl3): δ 7.69 (d, 2H, J = 8.4 Hz), 7.47 (d, 2H, J = 8.4 Hz), 4.42 (s, 4H), 3.85 (s, 4H), 2.41 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 144.4, 130.9, 130.2, 128.5, 79.1, 59.5, 37.3, 21.3.