Acetic Acid → 1-(4-fluoro-benzylamino)-1H-pyrrole-2-carboxylic acid allyl ester

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Reaction Conditions

Reaction Steps

Sodium cyanoborohydride (2.29 g, 36.4 mmol) was added to a solution of 1-amino-1H-pyrrole-2-carboxylic acid allyl ester (Example 1b, 3.03 g, 18.2 mmol), 4-fluorobenzaldehyde (1.96 mL, 18.3 mmol) and acetic acid (6 mL), in methanol (120 mL) at 25° C. The reaction mixture was stirred at 25° C. for 18 h, and then was concentrated in vacuo to a volume of about 30 mL. The remaining liquid was partitioned between half-saturated aqueous sodium bicarbonate solution (150 mL) and a 1:1 mixture of ethyl acetate and hexanes (2×200 mL). The organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. Purification of the residue by flash column chromatography (Merck silica gel 60, 40-63 μm, 0→40% ethyl acetate in hexanes) afforded the desired product, 1-(4-fluoro-benzylamino)-1H-pyrrole-2-carboxylic acid allyl ester (1.87 g, 6.8 mmol, 37% yield) as a clear liquid. 1H NMR (400 MHz, CDCl3) δ: 4.08 (2H, d, J=5.4 Hz), 4.75-4.77 (1H, m), 5.27-5.30 (1H, m), 5.37-5.41 (1H, m), 5.95-5.97 (1H, m), 5.98-6.05 (1H, m), 6.58-6.61 (1H, m), 6.75-6.76 (1H, m), 6.89-6.91 (1H, m), 6.97-7.01 (2H, m), 7.22-7.25 (2H, m).

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