反应详情

5-Bromo-6-(2,2,2-trifluoro-ethoxy)-nicotinic acid (75.0 g, 0.25 mol) was dissolved in DMF (850 mL). To the solution was added TBTU (91.0 g, 0.275 mol), N,N-diisopropylethyl amine (214 mL, 1.25 mol) and (1SR,2RS)-2-amino-cyclohexanol hydrochloride (41.7 g, 0.275 mol). The reaction mixture was stirred for 1.5 h at room temperature. The solvent was evaporated in vacuo, the residue was partitioned between ethyl acetate (2500 mL) and 1 N sodium hydroxide solution (2000 mL), the water phase was separated, extracted once more with ethyl acetate (1000 mL) and the organic phases were washed 2 times with water (2×1500 mL). Organic phases were pooled, dried with MgSO4 and concentrated to about 900 mL. The product precipitated upon stirring and cooling to 0° C. Filtration, washing with ethyl acetate/n-heptane (1:1) and drying in vacuo gave the title compound (81.1 g) as a white solid; MS (ISP) 397, 399 (M)+.

1. customThe solvent was evaporated in vacuo
2. customthe residue was partitioned between ethyl acetate (2500 mL) and 1 N sodium hydroxide solution (2000 mL)
3. customthe water phase was separated
4. extractionextracted once more with ethyl acetate (1000 mL)
5. washthe organic phases were washed 2 times with water (2×1500 mL)
6. dry with materialdried with MgSO4
7. concentrationconcentrated to about 900 mL
8. customThe product precipitated
9. stirringupon stirring
10. temperaturecooling to 0° C
11. filtrationFiltration
12. washwashing with ethyl acetate/n-heptane (1:1)
13. customdrying in vacuo