反应详情

In a 10 mL two-necked flask, the above synthesized 5-cyclopropyl-6-(2,2,2-trifluoroethoxy)nicotinic acid (50 mg, 191 μmol, Eq: 1.00) was combined with tetrahydrofuran (1.00 ml) and DMF (1 ml) to give a colorless solution. TBTU (92.2 mg, 287 μmol, Eq: 1.5) and N,N-diisopropylethylamine (124 mg, 167 μl, 957 μmol, Eq: 5) were added and the reaction mixture was stirred for 10 min at rt; then 1-(4-fluorophenyl)-1-methylhydrazine hydrochloride (40.6 mg, 230 μmol, Eq: 1.2; CAN 1978-54-7) was added and the reaction allowed to proceed over night at rt. The reaction mixture was then quenched with 1 M HCl (10 mL) and extracted with EtOAc (2×20 mL). The organic layers were washed with 1 M NaOH, then with H2O/NaCl solution. The organic layers were combined, dried over Na2SO4 and concentrated in vacuo. Purification by flash chromatography (silica gel, 10 g, 15% to 50% EtOAc in heptane) delivered finally 70 mg of the title product as white semisolid; MS (EI) 384.3 (M+H)+.

1. customto give a colorless solution
2. waitto proceed over night at rt
3. customThe reaction mixture was then quenched with 1 M HCl (10 mL)
4. extractionextracted with EtOAc (2×20 mL)
5. washThe organic layers were washed with 1 M NaOH
6. dry with materialdried over Na2SO4
7. concentrationconcentrated in vacuo
8. customPurification by flash chromatography (silica gel, 10 g, 15% to 50% EtOAc in heptane)