1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1-[2-(5-fluoro-1,3-dihydro-2H-isoindol-2-yl)-2-oxoethyl]-3-phenylpiperidin-2-one

Participants

Reaction Steps

To 2-(2-oxo-3-phenylpiperidin-1-yl)acetic acid (Example 91D, 0.168 g, 0.720 mmol) and 5-fluoroisoindoline hydrochloride (0.138 g, 0.792 mmol) in dichloromethane (0.5 mL) was added N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine (0.191 mL, 1.080 mmol), and the reaction was stirred at ambient temperature overnight. The reaction was loaded directly onto a SF15-12 silica gel column (Analogix®, Burlington, Wis.), and the title compound was eluted using a gradient of 5% to 100% ethyl acetate/hexanes over 20 minutes (flow=30 mL/minute). 1H NMR (300 MHz, CDCl3) δ ppm 7.14-7.36 (m, 6H), 6.92-7.02 (m, 2H), 4.85-4.90 (m, 2H), 4.78-4.83 (m, 2H), 4.43 (dd, J=15.6, 1.7 Hz, 1H), 4.06 (d, J=15.7 Hz, 1H), 3.73 (dd, J=7.7, 6.1 Hz, 1H), 3.65-3.71 (m, 1H), 3.57 (dt, J=11.6, 5.8 Hz, 1H), 2.19-2.29 (m, 1H), 1.97-2.11 (m, 2H), 1.83-2.00 (m, 1H); MS (DCI+) m/z 353 (M+H)+.

Provenance & Evidence