Chloroacetaldehyde → Ethyl 2-methyl-3-pyrrolecarboxylate

Participants

Reaction Steps

Ammonium hydroxide (28 to 30% (HCl titration (as NH3)), 290 mL, 4.3 mol) was added dropwise to a mixture of chloroacetaldehyde (50% wt aqueous solution, 182 mL, 1.43 mol) and ethyl acetoacetate (183 mL, 1.43 mol) at 0° C. The ice bath was removed, and the reaction mixture was stirred at ambient temperature overnight. The reaction mixture was extracted twice with ethyl acetate. The combined organic layers were washed with 2N hydrochloric acid and saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, and concentrated. The crude product was purified by flash chromatography eluting from silica gel with a gradient of 0-50% ethyl acetate in hexanes to afford 73.1 g of the title compound as a yellow solid. 1H NMR (200 MHz, CDCl3) δ 6.55 (2H, d, J=2.4 Hz), 4.26 (2H, q, J=7.4 Hz), 2.52 (3H, s), and 1.34 (3H, t, J=7.4 Hz).

Provenance & Evidence