反应详情

To a solution of 3,4-diethoxybenzoic acid (0.11 g; 0.52 mmol), and the product of Example 7, Step C (0.09 g; 10.52 mmol) in anhydrous THF (2 ml), PyBroP (0.25 g; 0.53 mmol) was added, followed by DIPEA (0.21 ml; 1.2 mmol), with stirring, at room temperature under N2. After overnight stirring, the mixture was diluted to 15 ml with EtOAc, washed with saturated NH4Cl (3×5 ml), brine, dried over anhydrous MgSO4 and filtered. The filtrate was evaporated to dryness under reduced pressure and the residue was purified by FCC (SiO2, EtOAc) to give the coupling product. This was suspended in anhydrous toluene (3 ml) and 1M TBAF was added. The resulting mixture was refluxed for 1 h under N2, cooled to room temperature and diluted to 15 ml with EtOAc, washed with H2O, brine, dried over anhydrous MgSO4, filtered and filtrate evaporated to dryness. The residue was purified by crystallization from MeOH, to give the title compound (0.096 g; 53%), as a colourless solid. 1H-NMR (CDCl3) 1.5 (m, 6H); 4.19 (m, 4H); 6.66 (s, 1H); 6.98 (d, 1H, J=8.4 Hz); 7.26 (m, 1H); 7.47 (d, 1H, J=8.5 Hz); 7.71 (d, 1H, J=1.8 Hz); 7.8 (dd, 1H, J=1.8, 8.5 Hz); 8.0 (dd, 1H, J=1.3, 8.5 Hz); 8.37 (broad s, 1H); 8.5 (s, 1H).

1. stirringAfter overnight stirring
2. washwashed with saturated NH4Cl (3×5 ml), brine
3. dry with materialdried over anhydrous MgSO4
4. filtrationfiltered
5. customThe filtrate was evaporated to dryness under reduced pressure
6. customthe residue was purified by FCC (SiO2, EtOAc)
7. customto give the coupling product
8. temperatureThe resulting mixture was refluxed for 1 h under N2
9. temperaturecooled to room temperature
10. washwashed with H2O, brine
11. dry with materialdried over anhydrous MgSO4
12. filtrationfiltered
13. customfiltrate evaporated to dryness
14. customThe residue was purified by crystallization from MeOH