反应详情

温度

-78 °C

To a stirred solution of piperazine-1,2,4-tricarboxylic acid 1-benzyl ester 4-tert-butyl ester 2-methyl ester (20.0 g, 53 mmol) in tetrahydrofuran (500 mL) under nitrogen was added N,N-dimethylformamide (50 mL). The reaction was cooled to about −78° C., and a 1 M solution of sodium bis(trimethylsilyl)amide in tetrahydrofuran (80 mL) was added. The reaction was stirred at about −78° C. for about 1 hour, and then benzyl bromide (9.4 mL, 79 mmol) was added. The reaction was stirred for about 30 minutes more at about −78° C., then warmed to room temperature and stirred overnight. The reaction was quenched with saturated sodium bicarbonate solution, and the mixture was extracted three times with ethyl acetate. The combined organic layers were extracted twice with water, brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to give 31 g of crude product. Purification by silica gel chromatography using 10-20% ethyl acetate/hexanes as eluent afforded the title compound of part 4-A (20.3 g, 82%): +APcI MS (M−tBu+H)+ 413, (M−Boc+H)+ 369; 1H NMR=400 MHz (CDCl3) δ: 7.37 (arom, m, 5H), 7.22 (arom, m, 3H), 7.00 (arom, m, 2H), 1.41 (BOC, d, 9H).

1. stirringThe reaction was stirred for about 30 minutes more at about −78° C.
2. temperaturewarmed to room temperature
3. stirringstirred overnight
4. customThe reaction was quenched with saturated sodium bicarbonate solution
5. extractionthe mixture was extracted three times with ethyl acetate
6. extractionThe combined organic layers were extracted twice with water, brine
7. dry with materialdried over anhydrous magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customto give 31 g of crude product
11. customPurification by silica gel chromatography