反应详情

To a solution of 4a (1.01 g, 2.62 mmol) in toluene (30 mL) at 0° C. were sequentially added DMF (0.2 mL) and oxalyl chloride (1.48 g, 11.66 mmol) dropwise. The mixture was allowed to warm to room temperature and stirred for 2 h, then transferred slowly to a mixture of 5i (0.56 g, 4.07 mmol) and triethylamine (0.42 g, 4.20 mmol) in THF (120 mL) at 0° C. After the mixture was warmed and stirred at room temperature for 15 h, water was added and the resulting mixture was extracted with ethyl acetate (2×30 mL). The combined extracts were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude amide (1.02 g) thus obtained was treated with a solution of POCl3 (1.25 g, 8.15 mmol) in dichloromethane (25 mL) at 80° C. for 4 h. The mixture was concentrated and poured into ice water. The resulting mixture was extracted with ethyl acetate (2×50 mL). The combined extracts were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated. Purification of the residue by flash chromatography on silica gel with ethyl acetate/hexanes (7:3) afforded 23 (0.62 g, 53%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.43 (br s, 1H), 7.32˜7.27 (m, 4H), 7.05 (d, 2H), 7.00 (br s, 1H), 2.38 (s, 3H), 1.81 (s, 6H); ESMS m/z: 447.0 (M+1).

1. customat 0° C.
2. temperatureAfter the mixture was warmed
3. stirringstirred at room temperature for 15 h
4. extractionthe resulting mixture was extracted with ethyl acetate (2×30 mL)
5. washThe combined extracts were washed with brine
6. dry with materialdried over anhydrous sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customThe crude amide (1.02 g) thus obtained
10. concentrationThe mixture was concentrated
11. additionpoured into ice water
12. extractionThe resulting mixture was extracted with ethyl acetate (2×50 mL)
13. washThe combined extracts were washed with brine
14. dry with materialdried over anhydrous sodium sulfate
15. filtrationfiltered
16. concentrationconcentrated
17. customPurification of the residue by flash chromatography on silica gel with ethyl acetate/hexanes (7:3)