Imidazole → HCID 86708513, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of benzyl 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate (0.7 g, 3.00 mmol) and methanamine (3.75 mL, 30.0 mmol) in ethanol (5 mL) was heated in a sealed reaction pressure vessel at 70° C. overnight. The reaction mixture was cooled to room temperature and concentrated to dryness. The residue was dissolved in dichloromethane (5.00 mL), triethylamine (0.502 mL, 3.60 mmol) and di-tert-butyl dicarbonate (0.766 mL, 3.30 mmol) were added and the reaction mixture was stirred at room temperature for 4 h. The reaction mixture was washed with water and brine, dried over magnesium sulfate and concentrated to give a colorless oil. The above oil was dissolved in DMF (5.00 mL), imidazole (0.409 g, 6.00 mmol) and tert-butyldimethylchlorosilane (0.678 g, 4.50 mmol) were added. The mixture was stirred at room temperature overnight. Water was added and the reaction mixture was extracted with ethyl acetate (3×), the organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo, the crude product was purified by flash chromatography on silica gel using an automated ISCO system (80 g gold column, eluting with 5-30% ethyl acetate/hexanes) to give (+/−)-(3R,4R)-benzyl 3-((tert-butoxycarbonyl)(methyl)amino)-4-((tert-butyldimethylsilyl)oxy)piperidine-1-carboxylate (Isomer A, 0.697 g) and (+/−)-(3R,4R)-benzyl 4-((tert-butoxycarbonyl)(methyl)amino)-3-((tert-butyldimethylsilyl)oxy)piperidine-1-carboxylate (Isomer B, 0.556 g). The structures were confirmed by NMR studies (1H-1D, 13C-1D, COSY, NOESY, dept-1H-13C-HSQC, 1H-13C-HMBC).

Provenance & Evidence