反应详情

To a solution of tert-butyl 3-oxoazetidine-1-carboxylate LII (2.0 g, 11.7 mmol) in THF (50 mL) under an argon atmosphere was added ZnI2 (0.11 mg, cat) followed by TMSCN (1.62 g, 16.4 mmol). The mixture was stirred at room temperature for 18 h, and was concentrated to dryness under reduced pressure. The residue was dissolved in EtOAc (100 mL), washed with aqueous NaHCO3 and water and then concentrated to dryness. The residue was dissolved in HOAc (25 mL) and treated with concentrated aqueous HCl (25 mL). The mixture was heated at reflux for 3 h and was concentrated to dryness. The residue was dissolved in iPrOH (20 mL) and 2 M aqueous NaOH (20 mL) followed by Boc2O (1.66 g, 8.0 mmol) were added. The iPrOH was removed with a rotary evaporator, water (30 mL) was then added to the residue and the mixture was extracted with Et2O (2×30 mL). The aqueous phase was acidified with 1 N aqueous HCl to pH=2 and extracted with EtOAc (3×30 mL). The organic phase was dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (100% EtOAc→1:1 EtOAc:MeOH) affording 1-(tert-butoxycarbonyl)-3-hydroxyazetidine-3-carboxylic acid LIII (0.17 g, 0.79 mmol, 7%). ESIMS found for C9H15NO5 m/z 216 (M−H)−.

1. concentrationwas concentrated to dryness under reduced pressure
2. dissolutionThe residue was dissolved in EtOAc (100 mL)
3. washwashed with aqueous NaHCO3 and water
4. concentrationconcentrated to dryness
5. dissolutionThe residue was dissolved in HOAc (25 mL)
6. additiontreated with concentrated aqueous HCl (25 mL)
7. temperatureThe mixture was heated
8. temperatureat reflux for 3 h
9. concentrationwas concentrated to dryness
10. dissolutionThe residue was dissolved in iPrOH (20 mL)
11. additionwere added
12. customThe iPrOH was removed with a rotary evaporator, water (30 mL)
13. additionwas then added to the residue
14. extractionthe mixture was extracted with Et2O (2×30 mL)
15. extractionextracted with EtOAc (3×30 mL)
16. dry with materialThe organic phase was dried over Na2SO4
17. filtrationfiltered
18. concentrationconcentrated under reduced pressure
19. customThe crude product was purified by column chromatography on silica gel (100% EtOAc→1:1 EtOAc:MeOH)