1-{[(1,1-diMethylethyl)oxy]carbonyl}-3-hydroxyazetidine-3-carboxylic acid

398489-26-4

7677-24-9

24424-99-5

1035351-06-4

Under argon protection, tert-butyl 3-oxoazetidine-1-carboxylate (2.0 g, 11.7 mmol) was dissolved in THF (50 mL), a catalytic amount of ZnI2 (0.11 mg) was added followed by the dropwise addition of trimethylcyanosilane (TMSCN, 1.62 g, 16.4 mmol). The reaction mixture was stirred at room temperature for 18 h and then concentrated under reduced pressure to remove the solvent. The residue was dissolved in EtOAc (100 mL), washed sequentially with saturated aqueous NaHCO3 and deionized water, and the organic phase was dried over anhydrous Na2SO4 and concentrated. The obtained residue was dissolved in acetic acid (HOAc, 25 mL), concentrated aqueous hydrochloric acid (25 mL) was added, and the mixture was heated at reflux for 3 hours and concentrated. The residue was dissolved in isopropanol (iPrOH, 20 mL) and 2M NaOH aqueous solution (20 mL) and di-tert-butyl dicarbonate (Boc2O, 1.66 g, 8.0 mmol) was added. After completion of the reaction, iPrOH was removed by rotary evaporation, water (30 mL) was added and extracted with ether (Et2O, 2 × 30 mL). The aqueous phase was acidified with 1N HCl aqueous solution to pH=2 and extracted with EtOAc (3×30 mL). The organic phases were combined, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (elution gradient: 100% EtOAc to 1:1 EtOAc:MeOH) to afford 1-(tert-butoxycarbonyl)-3-hydroxyazetidine-3-carboxylic acid (0.17 g, 0.79 mmol, 7% yield).ESMS analysis showed that the target compound, C9H15NO5, had a m/z of 216 (M-H)-.