Ethyl 3-bromopropionate → N-(2-Acetyl-3,4-dimethoxyphenyl)-β-alanine ethyl ester

Participants

Reaction Steps

Triethylamine (3.80 g, 5.35 mL, 38.46 mM) was at once added under N2 to a stirred mixture of 6'-amino-2',3'-dimethoxyacetophenone (2.5 g, 12.8 mM) and ethyl 3-bromopropionate (13.93 g, 9.86 mL, 76.93 mM) at room temperature. Immediately the reaction mixture solidified. This was heated under N2 to 135°-145° C. (bath temperature) for a period of 3 hours, while periodically stirring the solid reaction mixture to form a uniformly soft, semisolid mass. After cooling, the reaction was treated with 10% NaHCO3 (50 mL) and extracted with CH2Cl2 (3×60 mL). The organic layer, after the H2O wash, drying (Na2SO4), and the removal of the solvent in vacuo, gave a dark brown oily residue (5.3 g). This was chromatographed on a column of SilicAR CC-7 (350 g, 57 cm×5 cm) packed in hexane and eluted with increasing proportions of ethyl acetate/hexane, collecting 1 L fractions. Fraction 6, eluting with 15% ethyl acetate/hexane gave, upon removal of the solvent in vacuo, purified 6'-(N-2-carbethoxyethylamino)-2',3'-dimethoxyacetophenone (0.452 g, 12%) as a light yellow oil. IR (neat) μ: 2.97 (NH), 5.75 (C=O), 6.10.

Provenance & Evidence