Acetic Acid → 4-[(E)-3-(3,4-Dichloro-phenyl)-acryloyl]-1-(4-piperidin-1-yl-butyl)-piperazin-2-one

Participants

Reaction Conditions

Reaction Steps

Lithium aluminum hydride solution (1 M in tetrahydrofuran, 0.13 ml, 0.13 mmol) was added dropwise at −30° C. to a solution of 4-{4-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-2-oxo-piperazin-1-yl}-N-methoxy-N-methyl-butyramide (intermediate 5; 54 mg, 0.13 mmol), then after 10 min the reaction mixture was, cooled to −75° C. and acetone (161 mg, 2.8 mmol) was added. The homogeneous solution was allowed to reach room temperature over 16 h, then partitioned between water and ethyl acetate. The organic layer was washed with brine, dried (MgSO4), and evaporated. The crude aldehyde intermediate (4-{4-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-2-oxo-piperazin-1-yl}-butyraldehyde) and piperidine (10 mg, 0.12 mmol) were dissolved in 1,2-dichloroethane, then a freshly prepared solution of pyridine borane complex (8 M in pyridine, 30 μl, 0.33 mmol) and acetic acid (22 mg, 0.37 mmol) in ethanol (1 ml) was added dropwise at room temperature. The reaction mixture was stirred overnight, then volatile material was removed by rotary evaporation. The residue was purified by chromatography (SiO2; CH2Cl2/MeOH/NH4OH 90:10:0.25) to afford the title compound (28 mg, 51%). Light yellow gum, MS (ISP)=438.2 (M+H)+.

Provenance & Evidence