反应详情

A solution of methyl 5-({4-[(4-butylphenyl)ethynyl]benzyl}amino)-2-fluorobenzoate (305 mg; 0.73 mmol), formaldehyde (Aldrich, 50 μl; 1.84 mmol) and formic acid (2.5 mL) was stirred under microwaves at 100° C. for 5 min. The reaction mixture was then poured into an aqueous solution of NaOH 1M and extracted twice with EtOAc. The combined organic layers were washed with brine, dried over magnesium sulfate, filtrated and concentrated. Purification of the crude (257 mg, yellow oil) by flash chromatography on silicagel afforded 70 mg of the title compound as a yellow powder. HPLC, Rt: 5.84. min (purity=100%). 1H NMR (CDCl3) δ: 7.4 (m, 4H), 7.3 (s, 1H), 7.2 (m, 4H), 6.9 (t, J=7.8 Hz, 1H), 6.75 (m, 1H), 4.4 (s, 2H), 2.92 (s, 3H), 2.5 (t, J=7.7 Hz, 2H), 1.5 (m, 2H), 1.25 (m, 2H), 0.8 (t, J=7.53 Hz, 3H).

1. extractionextracted twice with EtOAc
2. washThe combined organic layers were washed with brine
3. dry with materialdried over magnesium sulfate
4. filtrationfiltrated
5. concentrationconcentrated
6. customPurification of the crude (257 mg, yellow oil) by flash chromatography on silicagel