Water → HCID 58128486, compound

Participants

Reaction Conditions

Reaction Steps

Commercially available tert-butyl 4-ethynylpiperidine-1-carboxylate was dissolved in 40 ml of THF and cooled to −78° C. forming a white slurry. Titrated n-BuLi (2.2 M in hexanes, 23.9 ml, 52.6 mmol) was added dropwise with stirring. The clear colorless solution was stirred at −78° C. for 5 minutes. A solution of the R-(+) benzyl glycidyl epoxide (8.63 g, 52.6 mmol) in THF (20 ml) was added dropwise. BF3 etherate (8.43 g, 59.7 mmol) was then added dropwise with a syringe and the solution stirred at −78° C. for 1 hour. Sat'd aq. NH4Cl was added (100 ml), the mixture warmed to RT, diluted with water to dissolve any remaining solids, and extracted with iPrOAc (3×100 ml). The organic fractions were combined, washed with brine, dried over MgSO4, filtered and stripped. Crude product was purified by chromatography on SiO2 eluting with 30% EtOAc:Hexanes. The alcohol was repurified by chromatography on a C18 reversed phase column (12-100% water:acetonitrile 0.1% TFA as two runs.). Product containing fractions were combined, reduced in volume by approximately 50%, —made basic by addition of sat'd aq. NaHCO3, water was added to dissolve some white solids, and the mixture extracted with iPrOAc (3×100). The organic fractions were combined, washed with brine, dried over MgSO4, filtered, and stripped.

Provenance & Evidence