Water → 3-[2-(2-Bromo-5-fluoro-phenoxymethyl)-phenyl]-acrylic acid ethyl ester

Participants

Reaction Steps

To a mixture of 1-bromo-4-fluoro-2-(2-iodo-benzyloxy)-benzene (0.29 mol, 117.4 g), sodium acetate (0.44 mol, 36.1 g, 1.5 equiv.), tetra-n-butylammonium bromide (0.29 mol, 90.3 g), palladium (II) acetate (8 mmol, 1.8 g, 3 mol %), and N-methylpyrrolidinone (900 mL) at 55-60° C., add drop wise a solution of ethyl acrylate (0.32 mol, 34.3 mL) in N-methylpyrrolidinone (200 mL). Cool the reaction mixture to room temperature and treat with water (2 L) and methyl tert-butyl ether (2 L). Pass through diatomaceous earth, add ethyl acetate (1 L), separate the layers, and wash with water (2 L). Dry the organic portion over anhydrous sodium sulfate, filter, and concentrate. Suspend the resulting solid in hexanes (1 L), refrigerate for 2 h, filter, and wash with cold hexanes (500 mL). Dry in a vacuum oven (50° C./20 mm Hg) to obtain the title compound as a pale yellow solid (104.4 g, 95%). LC-MS m/z 381.0 [M+H]+.

Provenance & Evidence