Ethyl Acetate → N-[4-(hydroxymethyl)phenyl]acrylamide

Participants

Reaction Conditions

Reaction Steps

p-Aminobenzyl alcohol (12.31 g, 100 mmol) was dissolved in a mixture of dichloromethane (200 mL) and tetrahydrofuran (20 mL) containing N,N-diisopropylethylamine (35 mL, 200 mmol). The resulting homogeneous solution was then cooled to 0° C. and acryloyl chloride (8.2 mL, 100 mmol) was added drop-wise over a 30-minute period while keeping the internal temperature of the reaction mixture below 20° C. The reaction mixture was stirred at 0° C. for about 60 minutes. The reaction mixture was poured into ice-cold 1M hydrochloric acid (0.6 L) and the organic layer was separated and evaporated to dryness to give a crude material (5 g) consisting primarily of the bis-acylated side product. The acidic aqueous layer was then extracted with ethyl acetate (2×200 mL) and the combined ethyl acetate layers were dried with sodium sulfate, filtered and concentrated under reduced pressure to provide a residue. Trituration of the residue with ethyl acetate yielded the title compound (10.5 g, 98.5% pure). An additional 2 g of the title compound were obtained by trituration of the crude material obtained from the dichloromethane layer.

Provenance & Evidence