反应详情

温度

25 °C

Sodium cyanoborohydride (1.11 g, 16.8 mmol) was added to a solution of 1-amino-1H-pyrrole-2-carboxylic acid allyl ester (Example 1b, 1.12 g, 6.74 mmol), 3-chloro-4-fluorobenzaldehyde (1.32 g, 8.08 mmol) and acetic acid (1.2 mL), in methanol (50 mL) at 25° C. The reaction mixture was stirred at 25° C. for 18 h, quenched with saturated aqueous sodium bicarbonate solution and was extracted with ethyl acetate (2×50 mL). The organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo. Purification of the residue by flash column chromatography (Teledyne Isco RediSep 40 g, 0→40% ethyl acetate in hexanes) afforded the desired product, 1-(3-chloro-4-fluoro-benzylamino)-1H-pyrrole-2-carboxylic acid allyl ester (1.36 g, 4.41 mmol, 65% yield) as an off-white oil. 1H NMR (400 MHz, CDCl3) δ 4.06 (2H, d, J=5.5 Hz), 4.76 (2H, d, J=5.3 Hz), 5.29 (1H, d, J=11.0 Hz), 5.40 (1H, d, J=16.4 Hz), 5.96-6.05 (2H, m), 6.58 (1H, t, J=5.5 Hz), 6.76 1H, (t, J=1.9 Hz), 6.91 (1H, dd, J1=4.3 Hz, J2=1.8 Hz), 7.06 (1H, t, J=8.6 Hz), 7.10-7.14 (1H, m), 7.33 (1H, dd, J1=7.1 Hz, J2=1.4 Hz).

1. customquenched with saturated aqueous sodium bicarbonate solution
2. extractionwas extracted with ethyl acetate (2×50 mL)
3. dry with materialThe organic layers were dried over magnesium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customPurification of the residue by flash column chromatography (Teledyne Isco RediSep 40 g, 0→40% ethyl acetate in hexanes)