tert-Butyl 4-oxopiperidine-1-carboxylate → tert-Butyl 4-(2-(I-benzylpiperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6-dihydropyridine-1(2H)-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of Compound 14A (0.68 g, 1.686 mmol) in dry THF (9.4 ml) at −78° C. under argon was added dropwise BuLi (0.742 ml, 1.855 mmol). After the completion of addition, the reaction mixture was stirred at −78° C. for 1 h. At the conclusion of this period, a solution of tert-butyl 4-oxopiperidine-1-carboxylate (0.37 g, 1.855 mmol) in THF (1.9 ml) was transferred to the reaction mixture via cannulation. The resulting mixture was stirred and gradually warmed to −20° C., where it stirred for an additional hour. At the conclusion of this period, the mixture was quenched with aq. NaHCO3 (saturated, 20 mL) and then extracted with EtOAc (3×15 mL). The combined organic layers were washed with H2O (3×10 mL) and brine (10 mL), dried (Na2SO4) and then filtered. The solvent was removed under reduced pressure, and the resulting residue was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0 to 60% EtOAc) to give Compound 14B′ as a white solid (0.63 g, 68% yield). 1H NMR (500 MHz, chloroform-d) δ ppm 7.78 (d, J=1.7 Hz, 1H), 7.62 (d, J=8.5 Hz, 1H), 7.43 (dd, J=8.5, 1.9 Hz, 1H), 7.30-7.36 (m, 4H), 7.24-7.29 (m, 1H), 5.21 (tt, J=7.9, 3.9 Hz, 1H), 3.98 (br. s., 2H), 3.54 (s, 2H), 3.25 (br. s., 2H), 2.73 (br. s., 2H), 2.38 (t, J=8.7 Hz, 2H), 2.08-2.18 (m, 2H), 1.85-2.03 (m, 5H), 1.75 (d, J=12.1 Hz, 2H), 1.47-1.50 (m, 9H). LC/MS (m/z)=524 (M+H)+.

Provenance & Evidence