反应详情

A solution of ethyl 1-benzyl-4-hydrazino-piperidin-4-ylcarboxylate dihydrochloride salt (D27, 3.0 g, 0.0086 mol) in methanol (100 ml) under nitrogen was treated with methyl acetimidate hydrochloride (940 mg, 0.0086 mol) and triethylamine (3.7 ml, 0.026 mol) and stirred at room temperature for 3 h. The solution was concentrated in vacuo at below 30° C. and the residue treated with triethylorthoformate (50 ml) and pyridine (5 ml) and the heterogenous mixture stirred for 18 h at room temperature, followed by heating under reflux for 1.5 h. The mixture was concentrated in vacuo and the residue treated with potassium carbonate solution (30 ml) and extracted with ethyl acetate (2×40 ml). The combined extracts were dried (Na2SO4) and concentrated in vacuo to leave a dark red oil, which was chromatographed on silica gel eluting initially with ether, then with 1:1 ethyl acetate/ether to afford the title compound (D30) as a yellow oil (430 mg, 15%).

1. concentrationThe solution was concentrated in vacuo at below 30° C.
2. additionthe residue treated with triethylorthoformate (50 ml) and pyridine (5 ml)
3. stirringthe heterogenous mixture stirred for 18 h at room temperature
4. temperatureby heating
5. temperatureunder reflux for 1.5 h
6. concentrationThe mixture was concentrated in vacuo
7. additionthe residue treated with potassium carbonate solution (30 ml)
8. extractionextracted with ethyl acetate (2×40 ml)
9. dry with materialThe combined extracts were dried (Na2SO4)
10. concentrationconcentrated in vacuo
11. customto leave a dark red oil, which
12. customwas chromatographed on silica gel eluting initially with ether