反应详情

温度

50 °C

To solution of methyl 5-({4-[(4-butylphenyl)ethynyl]benzyl}amino)-2-fluorobenzoate (500 mg; 1.20 mmol) in anhydrous DCE (30 mL) were added ethyl-2-formyl-1-cyclopropanecarboxylate (Aldrich, 0.40 mL; 3.01 mmol), triacetoxyborohydride (382 mg; 1.81 mmol).The resulting mixture was stirred at 50° C. under N2 atmosphere for 4 hours. The mixture was poured into a saturated solution of NaHCO3 (50 mL) and extracted with DCM (2×50 mL). The combined organic layers were washed with brine (100 mL), dried over magnesium sulfate, filtrated and the solvents were removed under reduced pressure to give 872 mg. Purification of this crude by flash chromatography on silicagel (c-Hex/EtOAc, gradient 95:5 to 90:10) gave 340 mg (65%) of the title compound as a yellow oil. HPLC, Rt: 6.06 min (purity=96.2%). LC/MS, M+(ESI): 542.3. 1H NMR (CDCl3) δ: 7.43 (t, J=8.5 Hz, 4H), 7.32 (m, 1H), 7.22 (d, J=7.9 Hz, 2H), 7.15 (d, J=7.9 Hz, 2H), 6.93 (m, 2H), 4.54 (s, 2H), 4.08 (m, 2H), 3.89 (s, 3H), 3.35 (m, 2H), 2.61 (t, J=7.5 Hz, 2H), 1.32-1.58 (m, 7H), 1.24 (t, J=7.0 Hz, 3H), 0.92 (t, J=7.3 Hz, 3H), 0.88 (m, 1H).

1. customresulting mixture
2. extractionextracted with DCM (2×50 mL)
3. washThe combined organic layers were washed with brine (100 mL)
4. dry with materialdried over magnesium sulfate
5. filtrationfiltrated
6. customthe solvents were removed under reduced pressure
7. customto give 872 mg
8. customPurification of this crude by flash chromatography on silicagel (c-Hex/EtOAc, gradient 95:5 to 90:10)