1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1-(tert-butoxycarbonyl)-4-[[N-(3-(trifluoromethyl)benzoyl)glycyl]aminomethyl]piperidine

Participants

Reaction Conditions

Reaction Steps

N-[3-(Trifluoromethyl)benzoyl]glycine (4.22 g, 17.0 mmol), EDCI (4.25 g, 22.1 mmol), 1-hydroxybenzotriazole hydrate (2.99 g, 22.1 mmol) and triethylamine (1.72 g) were added to an anhydrous dichloromethane (200 mL) solution of 1-(tert-butoxycarbonyl)-4-(aminomethyl)piperidine (4.03 g). The resulting reaction mixture was stirred at 25° C. for 20 hours, and H2O (100 mL) was then added to the mixture. The obtained mixture was extracted with dichloromethane (50 mLX 2). The extracts were combined, washed with H2O (50 mL×2) and brine (50 mL), dried (over MgSO4) and concentrated to thereby afford a yellow oil. The obtained crude product was purified by column chromatography (SiO2,70% ethyl acetate-hexane) to provide 1-(tert-butoxycarbonyl)-4-[[N-(3-(trifluoromethyl)benzoyl)glycyl]aminomethyl]piperidine as a white solid (6.39 g, 85%). 1H NMR (CDCl3, 300 MHz) δ 1.4 (s, 9H), 1.0-1.8 (m, 5H), 2.6-2.8 (m, 2H), 3.15-3.3 (m, 2H), 4.0-4.3 (m, 4H), 6.6-6.7 (m, 1H), 7.64 (s, 1H), 7.60 (dd, 1H, J=7.2, 7.2 Hz), 7.79 (d, 1H, J=7.2 Hz), 8.0 (d, 1H, J=7.2 Hz), 8.11 (s, 1H). The purity was determined by RPLC/MS (97%). ESI/MS m/e 444.3 (M++H, C21H28N3O4).

Provenance & Evidence