反应详情

温度

25 °C

Part A: To a solution of ethyl 3,3-diethoxypropionate (90% tech.) (5.28 g, 25 mmol) in 50 mL of THF was added 1.00 N sodium hydroxide in water (25.00 mL, 25 mmol), and the resulting mixture was stirred at 25° C. for 18 h. The mixture then was concentrated under vacuum to afford a residual white solid. This solid was dissolved in 50 mL of DMF. To the solution was added EDCI (5.75 g, 30.0 mmol), 1-hydroxybenzotriazole (4.56 g, 33.8 mmol), and benzyl piperazine-1-carboxylate (5.51 g, 25.0 mmol), and the resulting mixture was stirred at 25° C. for 24 h. The reaction mixture was concentrated under vacuum, and the residue was diluted with water. The aqueous mixture was extracted with ethyl acetate, and the combined extracts were washed aqueous sodium bicarbonate solution and brine, dried over anhydrous sodium sulfate, filtered, and concentrated. Column chromatography on silica gel (elution: 10-40% ethyl acetate/chloroform) furnished 8.00 g (88%) of benzyl 4-(3,3-diethoxypropanoyl)piperazine-1-carboxylate as an oil; 1H NMR (500 MHz, CDCl3) δ 57.34 (m, 5H), 5.14 (s, 2H), 4.90 (t, 1H, J=5.5 Hz), 3.73-3.46 (m, 12H), 2.68 (d 2H, J=5.5 Hz), 1.19 (t, 6H, J=7.0 Hz).

1. concentrationThe mixture then was concentrated under vacuum
2. customto afford a residual white solid
3. stirringthe resulting mixture was stirred at 25° C. for 24 h
4. concentrationThe reaction mixture was concentrated under vacuum
5. additionthe residue was diluted with water
6. extractionThe aqueous mixture was extracted with ethyl acetate
7. washthe combined extracts were washed aqueous sodium bicarbonate solution and brine
8. dry with materialdried over anhydrous sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated