Diisopropylethylamine → HCID 86659595, compound

Participants

Reaction Steps

To a solution of (2S,5R)-6-(phenylmethoxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid (2.108 g, 7.63 mmol) in anhydrous dimethylformamide (15 mL) was added BOP (4.05 g, 9.15 mmol) and the resulting mixture was stirred at room temperature under nitrogen for 5 minutes. Diisopropyl ethyl amine (2.66 mL, 15.26 mmol) was then added followed by a solution of tert-butyl (3R,4S)-4-amino-3-fluoropiperidine-1-carboxylate (1.665 g, 7.63 mmol) in 20 mL of dichloromethane. The resulting solution was stirred at room temperature under nitrogen for 2 hours then concentrated under vacuum and the residue partitioned between ethyl acetate and water. The aqueous layer was washed twice with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, and concentrated under vacuum. The residue was purified via silica gel flash chromatography (Isco Combiflash apparatus—120 g silica gel, 80 mL/min, 254 nM, 0% to 100% EtOAc/hexane over 6 column volumes then 100% EtOAc for 9 column volumes; title compound eluted at 100% EtOAc). Fractions containing pure title compound were collected and concentrated in vacuo to give a tan solid. Fractions containing impure product were also collected and repurified by HPLC (30×100 mm Sunfire column, 5 microns, 35 mL/min, 10% to 100% CH3CN+0.1% TFA/water+0.1% TFA over 15 min.; title compound eluted at 70% CH3CN+0.1% TEA). Fractions containing pure product were combined and concentrated in vacuo. The resulting aqueous residue was then extracted with ethyl acetate. The organic layer was collected and dried over magnesium sulfate. Concentration in vacuo gave a white solid which was combined with the material isolated from silica gel chromatography to afford the title compound.

Provenance & Evidence