1-Piperidinecarboxaldehyde → tert-Butyl 2-formyl-6-phenylpyridin-3-ylcarbamate

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

A solution of 1D (1.75 g, 5 mmol) in dry THF (50 mL) under argon was cooled to −72° C. and treated dropwise with n-butyllithium (2.5 M in hexanes, 4 mL, 10 mmol) at such a rate so that the temperature did not exceed −65° C. Upon completion of the addition, the reaction was stirred at −72° C. for an additional hour. N-formyl piperidine (1.1 mL, 10 mmol) was added, and then the reaction was allowed to warm up to 0° C. and maintained there for an hour. The solution was quenched by the addition of 1 M aqueous HCl to bring the pH to 6-8. The reaction was stirred at RT for 5 min, extracted with EtOAc (3×50 mL). The combined organic layers were washed with saturated NaCl, dried over Na2SO4, filtered, and evaporated under reduced pressure. The residue was purified by silica gel (110 g) column chromatography, eluting with a gradient of EtOAc (0-30%) in hexane to give the title compound as a yellow solid (1.02 g, 68%). LC/MS (method A): retention time=4.24 min, (M+H-tBu)+=243. 1H NMR (CDCl3, 400 MHz): δ 10.25 (s, 1H), 10.15 (s, 1H), 8.86 (d, J=9.0 Hz, 1H), 8.00-8.02 (m, 2H), 7.87(d, J=9.0 Hz, 1H), 7.38-7.47 (m, 3H) 1.56 (s, 9H). 13C NMR (100 MHz, CDCl3): δ 197.93, 153.16, 151.18, 138.26, 138.14, 136.51, 129.45, 129.27, 127.50, 126.78, 125.80, 82.03, 28.64.

Herkunft & Nachweise