Sodium hydride → 1-(t-Butoxycarbonyl)-4-(3-oxo-3-(3-pyridyl)prop-1-enyl)piperidine

Participants

Reaction Conditions

Reaction Steps

A solution of dimethyl (2-oxo-2-(3-pyridyl)ethyl)phosphonate (150 mg, 0.65 mmol, from EXAMPLE 213, Step A) in THF (1.8 mL) was added to a stirred suspension of sodium hydride (60% oil dispersion, 15 mg of NaH, 0.63 mmol) in THF (3.0 mL). The resulting suspension was warmed in a 45° C. oil bath for 30 min. After the mixture had cooled to RT, 1-(t-butoxycarbonyl)-4 piperidinecarboxaldehyde (112 mg, 0.53 mmol) was added in THF (1.5 mL). After stirring overnight at RT, the mixure was diluted with ether (20 mL) and washed with 2.5 N NaOH (20 mL) followed by saturated aq. NaCl (20 mL). The aq. layers were extracted in succession with ether (20 mL), and the combined organic layers were dried (Na2SO4), decanted, and evaporated. Purification by flash column chromatography on silica gel, eluting with 80:20 v/v to 60:40 v/v hexanes/EtOAc, gave 135 mg of the title compound (trans isomer) as a yellow syrup. For the title compound: 1H NMR (500 M , CDCl3) δ 9.17-9.13 (bs, 1H), 8.81 (bd, J=4, 1H), 8.27 (d, J=8, 1H), 7.49 (dd, J=8, 4, 1H), 7.07 (dd, J=15, 7, 1H), 6.85 (dd, J=15, 1, 1H), 4.254.13 (bs, 2H), 2.87-2.78 (m, 2H), 2.51-2.41 (m, 1H), 1.83 (d, J=12, 2H), 1.49 (s, 9H), 1.45 (qd, J=12, 4, 2H); ESI-MS 261 (M+H−56), 217 (M+H−100); HPLC A: 1.73 min.

Provenance & Evidence