反应详情

温度

0 °C

The title compound was prepared according to the procedure described by John S. Kiely and Stephen R. Priebe in Organic Preparations and Procedures Int., 22 (6), 761-768 (1990). Thus dicyclohexylcarbodiimide (9.33 g, 45.2 mmol) in methylene chloride (0.5M) was added to methylene chloride (250 mL). This solution was cooled to 0° C. under nitrogen and Boc-L-norleucine (10.5 g, 45.2 mmol) was added. The resulting slurry was stirred for 5 min, and then ethyl N-benzylglycinate (8.72 g, 45.2 mmol) was added. The reaction was stirred for 2 h at 0° C., then at 20° C. overnight. The precipitate was removed by filtration, and hydrogen chloride gas bubbled through the methylene chloride solution for 2-4 h, until the reaction was shown to be complete by tic. The solvent was removed in vacuo, and the residue partitioned between ethyl acetate (150 mL) and saturated sodium bicarbonate solution (42 mL). The organic phase was washed with saturated sodium chloride, dryed over magnesium sulfate, filtered and evaporated. The crude diketopiperazine was triturated with hexane to give the title compound as a white powder. 1HNMR (300 MHz, CDCl3) δ 7.24-7.40 (5H, m), 6.22 (1H, br s), 4.07 (1H, dt, J=3, 6 Hz), 3.87 (1H, d, J=17 Hz), 3.80 (1H, d, J=17 Hz), 1.88 (2H, m), 1.35 (4H, m), 0.91 (3H, t, J=7 Hz).

1. customThe title compound was prepared
2. stirringThe reaction was stirred for 2 h at 0° C.
3. customat 20° C.
4. customovernight
5. customThe precipitate was removed by filtration, and hydrogen chloride gas
6. custombubbled through the methylene chloride solution for 2-4 h, until the reaction
7. customThe solvent was removed in vacuo
8. customthe residue partitioned between ethyl acetate (150 mL) and saturated sodium bicarbonate solution (42 mL)
9. washThe organic phase was washed with saturated sodium chloride
10. filtrationfiltered
11. customevaporated
12. customThe crude diketopiperazine was triturated with hexane