Glycolic Acid → 4-(5-Hydroxymethyl-[1,2,4]oxadiazol-3-yl)-piperidine-1-carboxylic acid tert-butyl ester

To a solution of hydroxy-acetic acid (1.67 g, 22 mmol), NEt3 (4.4 g, 44 mmol) in toluene (150 mL) was added isobutylchloroformate (6 g, 44 mmol) at 0° C. The mixture was stirred at room temperature for 1.5 hours. 4-(N-Hydroxycarbamimidoyl)-piperidine-1-carboxylic acid tert-butyl ester (5.35 g, 22 mmol) was added to the mixture. The mixture was heated under reflux overnight, and then cooled to room temperature; the mixture was washed successively with H2O and brine. After drying (Na2SO4), the solvent was removed. The residue was dissolved in THF (20 mL), and aqueous NaOH (10 mL, 10 mmol) was added. The mixture was stirred at room temperature for 2 hours and diluted with EtOAc (50 mL). The organic layer was washed with brine, after drying (Na2SO4), the solvent was removed in vacuo, and the residue was purified by silica column chromatography with EtOAc/hexanes to afford the desired product.

1. temperatureThe mixture was heated
2. temperatureunder reflux overnight
3. temperaturecooled to room temperature
4. washthe mixture was washed successively with H2O and brine
5. dry with materialAfter drying (Na2SO4)
6. customthe solvent was removed
7. dissolutionThe residue was dissolved in THF (20 mL)
8. stirringThe mixture was stirred at room temperature for 2 hours
9. washThe organic layer was washed with brine
10. dry with materialafter drying (Na2SO4)
11. customthe solvent was removed in vacuo
12. customthe residue was purified by silica column chromatography with EtOAc/hexanes

ORD record

ord-15a7d72813cc4e648eae5d151b752172

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08288384B2