反应详情

温度

0 °C

(R)-2-Cyclohexylmethyl-4-morpholin-4-yl-4-oxo-butyric acid (0.20 g, 0.71 mmol) (see Example 1-part a and b) was dissolved in 5 mL of DMF and cooled to 0° C. by an ice-water bath. EDC (0.18 g, 0.92 mmol) and 1-hydroxybenzotriazole (0.12 g, 0.92 mmol) were added and stirring, under argon, continued for 25 min. Then 4-amino-4-cyano-1-methylpiperidine (0.098 g, of the mixture of aminonitrile:cyanohydrin:ketone) was dissolved in 1 mL of DMF and added to the solution of the active ester. The resulting mixture was stirred at ambient temperature for 4 h. The volatiles were removed in vacuo and the resulting residue was dissolved in 100 mL of EtOAc and washed sequentially with 2×100 mL of saturated sodium bicarbonate and 1×100 mL of brine. The organic layer was dried over MgSO4, filtered, and concentrated to a thick oil. The oil was purified by column chromatography on SiO2 using as eluent 5% MeOH in CH2Cl2 to give the title compound as a clear oil (0.005 g): 1H NMR (CDCl3) 6.64 (1H, m), 3.73-3.37 (8H, m), 2.95-2.85 (1H, m), 2.75-2.55 (2H, m), 2.5-2.37 (2H, m), 2.34-2.25 (3H, m), 1.98-1.82 (2H, m), 1.80-1.58 (6H, m), 1.32-1.10 (8H, m), 0.95-0.78 (3H,m). MS: m/z=405 M+1.

1. stirringThe resulting mixture was stirred at ambient temperature for 4 h
2. customThe volatiles were removed in vacuo
3. dissolutionthe resulting residue was dissolved in 100 mL of EtOAc
4. washwashed sequentially with 2×100 mL of saturated sodium bicarbonate and 1×100 mL of brine
5. dry with materialThe organic layer was dried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated to a thick oil
8. customThe oil was purified by column chromatography on SiO2 using as eluent 5% MeOH in CH2Cl2