Trimethylsilyl cyanide → 1-[(Tert-butoxy)carbonyl]-3-hydroxyazetidine-3-carboxylic acid

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Reaction Steps

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)−.

Provenance & Evidence