22264-50-2

845621-11-6

22264-50-2

1. 1-carbamoyl-cyclobutanecarboxylic acid (1.43 g, 10.0 mmol, 1 eq.) was dissolved in a water-ice bath under nitrogen protection and 1N aqueous NaOH solution (10 mL, 10.0 mmol, 1 eq.) was added slowly. 2. NaOCl solution (10-13% solution, 9.0 mL, ~15.0 mmol, 1.5 eq.) was added slowly and the reaction mixture was stirred for 1 hour at 5 °C. 3. 10N NaOH solution (2.0 mL, 20 mmol, 2 eq.) was added slowly, keeping the reaction temperature below 20 °C and stirred at 15-25 °C for 3 h. The reaction was monitored by LC-MS. The completion of the reaction was monitored by LC-MS. 4. Quench the reaction with an aqueous solution (3 mL) of Na2S2O3-3H2O (2.48 g, 10 mmol, 1 eq.) at 15 °C and continue stirring for 1 hour. 5. Neutralize the reaction mixture with 12N HCl aqueous solution to pH=7.0. 6. Volatiles were removed by azeotropic distillation with toluene under reduced pressure to give about 9 g of white solid. 7. The solid was extracted with methanol (3 x 30 mL) and 2.0 g of crude product was obtained after evaporation of methanol. 8. By 1H NMR analysis, it was determined that the solid contained 0.81 g of the target product, 1-aminocyclobutanecarboxylic acid (70% yield), and the rest were inorganic salts. 9. Comparison of 1H and 13C NMR data confirmed that the structure of the product was consistent with the standard sample provided by Sumitomo Chemical, Inc.