Acetic Acid → tert-Butyl trans(+/-)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-(ethylamino)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A 2 N ethylamine/tetrahydrofuran solution (5 mL) was added to tert-butyl 4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-oxopiperidine-1-carboxylate obtained in Example (201c) (102 mg, 0.275 mmol), and the mixture was heated under reflux at 70° C. for four hours. The reaction solution was concentrated under reduced pressure, and then tetrahydrofuran (2 mL) and methanol (2 mL) were added. A 2 N ethylamine-tetrahydrofuran solution (138 μL), sodium cyanoborohydride (86.4 mg, 1.38 mmol) and acetic acid (110 μL, 1.93 mmol) were added, and the mixture was stirred at room temperature for 15 hours. The reaction solution was concentrated under reduced pressure, and aqueous saturated sodium bicarbonate solution was added to the residue, followed by extraction with chloroform. The resulting organic layer was dried over anhydrous sodium sulfate, and then the insoluble matter was separated by filtration. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (eluent: chloroform:methanol=10:1 v/v) to obtain 46 mg of the cis isomer of the title compound (42%) as a pale yellow oily substance and 51 mg of the trans isomer of the title compound (46%) as a pale yellow oily substance.

Provenance & Evidence