2-Aminoadamantane hydrochloride → HCID 66954042, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-aminoadamantane hydrochloride (4.17 g, 22 mmol) and DIEA (28.7 g, 223 mmol) in anhydrous CH2Cl2 (40 mL) was added CDI (4.33 g, 27 mmol) at 0° C. and then stirred for 1 h at 0° C. under N2 atmosphere. Ethyl 2-(7-bromospiro[indene-1,4′-piperidine]-3(2H)-ylidene)acetate (7.77 g, 22 mmol) in CH2Cl2 anhydrous (40 mL) was added dropwise to the above mixture. The mixture was stirred for 8 h at rt under N2. The reaction mixture was washed with 1 N aq HCl. The organic layer was dried over Na2SO4, filtered and concentrated to leave a residue, which was purified by silica gel column chromatography to afford ethyl 2-(7-bromo-1′-(2-adamantylcarbamoyl)spiro[indene-1,4′-piperidine]-3(2H)-ylidene)acetate (4.1 g, 35%). Preparative SFC using a ChiralCel-OJ, 400×25 mm I.D, 20 μm (Daicel Chemical Industries, Ltd) column maintained at 35° C. eluted with 75:25 supercritical CO2/MeOH at a flow rate of 70 mL min−1 and a nozzle pressure of 100 bar afforded two isomers.

Provenance & Evidence