反应详情

温度

70 °C

A solution of methyl 5-amino-2-fluorobenzoate (500 mg, 2.96 mmol), 4-(phenylethynyl)benzaldehyde (6 10 mg, 2.96 mmol) and acetic acid (0.25 mL, 4.40 mmol) in toluene (20 mL) was heated under reflux for 3 h with azeotropic removal of water. Then the solvent was removed by distillation at atmospheric pressure and replaced by anhydrous DCE (20 mL). Butanal (Fluka, 0.66 mL, 7.39 mmol), sodium triacetoxyborohydride (1880 mg, 8.87 mmol) and acetic acid (0.25 mL, 4.40 mmol) were added and the resulting mixture was heated at 70° C. After 45 min, an additional amount of sodium triacetoxyborohydride (630 mg, 2.96 mmol) was added. After 45 min, the reaction mixture was diluted with water (40 mL) and extracted with DCM (3×20 mL). The combined organic layers were dried over MgSO4 and the solvents were removed under reduced pressure. Purification by flash chromatography on silicagel (cHex/EtOAc): gave. 924 mg (75%) of the title compound as a colorless oil. HPLC, Rt: 5.6 min (purity: 99.8%). LC/MS, M+(ESI): 416.1. 1H NMR (CDCl3) δ: 7.51-7.44 (m, 4H), 7.32 (m, 3H), 7.17 (m, 3H), 6.92 (dd, J=9.8, 9.7 Hz, 1H), 6.73 (m, 1H), 4.49 (s, 2H), 3.88 (s, 3H), 3.36 (t, J=7.2 Hz, 2H), 1.60 (m, 2H), 1.34 (m, 2H), 0.93 (t, J=7.2 Hz, 3H).

1. customThen the solvent was removed by distillation at atmospheric pressure
2. waitAfter 45 min
3. extractionextracted with DCM (3×20 mL)
4. dry with materialThe combined organic layers were dried over MgSO4
5. customthe solvents were removed under reduced pressure
6. customPurification by flash chromatography on silicagel (cHex/EtOAc)
7. customgave