Diisopropylethylamine → Tert-butyl 4-(5-(ethoxycarbonyl)pyridin-2-yl)piperazine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of ethyl 6-chloronicotinate (2.67 g, 14.4 mmol), tert-butyl piperazine-1-carboxylate (2.5 g, 13.4 mmol) and N,N-diisopropylethylamine (3.5 mL, 20 mmol) in DME (15 mL) was heated at 120° C. for 12 hours. The mixture was then cooled to room temperature and partitioned with ethyl acetate and 10% aqueous citric acid. The organic layer was washed twice with 10% aqueous citric acid then brine and dried over anhydrous sodium sulfate. Filtration and concentration followed by silica gel flash chromatography of the residue using 3:1 hexanes:ethyl acetate to 100% ethyl acetate afforded tert-butyl 4-(5-(ethoxycarbonyl)pyridin-2-yl)piperazine-1-carboxylate (3.65 g). 1H NMR (400 MHz, CDCl3): 8.81 (s, 1H), 8.04 (d, 1H), 6.58 (d, 1H), 4.33 (q, 2H), 3.70-3.67 (m, 4H), 3.56-3.53 (m, 4H), 1.49 (s, 9H), 1.37 (tr, 3H).

Provenance & Evidence