Sodium Hydroxide → ethyl 1-(5-chloro-2-nitrobenzyl)-4-methyl-1H-pyrrole-2-carboxylate

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Reaction Steps

Vigorously stir a solution of 2-(bromomethyl)-4-chloro-1-nitro-benzene (25.02 g, 99.88 mmoles) in DCM (200 mL), and to this add a solution of ethyl 4-methyl-1H-pyrrole-2-carboxylate (15 g, 97.92 mmoles) in DCM (200 mL). Then add 30-hydrated tetra-n-butylammonium hydroxide (0.508 g) and cool the stirred mixture under nitrogen to 5° C. using an external ice-bath. Add 25% aq. sodium hydroxide (200 mL) dropwise over 15 minutes observing the internal temperature rise to 10° C. Stir and allow to warm to room temperature. Stir at room temperature for 3.5 h. Add further 50% aq. sodium hydroxide (20 mL) and stir at room temperature for a further 1 h. Stop the stirring and allow the layers to separate. Transfer to a separating funnel and wash the organic layer with 1N hydrochloric acid (200 mL), observing the pH of this layer to be acidic using indicator paper. Next wash the organic layer with water (600 mL) and then brine (600 mL) and finally dry over Na2SO4. Filter the mixture and remove the solvent in vacuo at 40° C. to give an orange oil. Purify by passing through a silica gel pad with iso-hexane/ethyl acetate (gradient eluting from 10 to 20%) to give ethyl 1-(5-chloro-2-nitrobenzyl)-4-methyl-1H-pyrrole-2-carboxylate as a yellow oil (33 g, quantitative). MS (m/z): 322.98 (M+1).

Provenance & Evidence