反应详情

6-Chloro-5-(4-chloro-phenyl)-nicotinic acid (1.4 g, 5 mmol) was dissolved in N,N-dimethylformamide (30 mL). To this solution was added sequentially (1R,2R)-2-amino-cyclohexanol hydrochloride (0.87 g, 6 mmol), TBTU (1.84 g, 6 mmol), and N-ethyldiisopropylamine (4.47 mL, 26 mmol). The reaction mixture was stirred at room temperature for 72 hours then concentrated in vacuo. The residue was then dissolved in ethyl acetate (100 mL) and washed with 0.5 N HCl (100 mL), saturated sodium bicarbonate (100 mL) and water (100 mL). The aqueous phases were extracted with ethyl acetate (2×100 mL), the organics were combined and the whole was dried over MgSO4 and concentrated in vacuo. The solid residue was purified by stirring with (ethylacetate/heptane 1:2, 50 mL) to give 6-chloro-5-(4-chloro-phenyl)-N-((1R,2R)-2-hydroxy-cyclohexyl)-nicotinamide as a colorless solid, 1.4 g (73% yield). m/z (ISP+): 364.9, 366.9 (M+H).

1. concentrationthen concentrated in vacuo
2. dissolutionThe residue was then dissolved in ethyl acetate (100 mL)
3. washwashed with 0.5 N HCl (100 mL), saturated sodium bicarbonate (100 mL) and water (100 mL)
4. extractionThe aqueous phases were extracted with ethyl acetate (2×100 mL)
5. dry with materialthe whole was dried over MgSO4
6. concentrationconcentrated in vacuo
7. customThe solid residue was purified
8. stirringby stirring with (ethylacetate/heptane 1:2, 50 mL)