Ammonium Chloride → 3-(4-Bromo-thiophen-2-yl)-acrylic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

[Bis-(2,2,2-trifluoro-ethoxy)-phosphoryl]-acetic acid methyl ester (9.25 g, 29.1 mmol) was dissolved in THF (400 ml) and 18-C-6 (13.9 g, 52.4 mmol) was added and the mixture was cooled to −78° C. Next, KHMDS (5.73 g, 28.8 mmol) was added and the reaction mixture was stirred for 30 minutes, after which 4-bromothiophene-2-carboxaldehyde (5.0 g, 26.2 mmol) was added and the reaction was stirred for an additional 3 hours. Saturated NH4Cl (100 ml) was added and the reaction was warmed to 22° C. The mixture was diluted with EtOAc (700 ml) and H2O (400 ml). The organic layer was washed 10% HCl (100 ml), brine (100 ml), and dried (MgSO4). The solvent was evaporated in vacuo and the crude residue was purified by silica-gel chromatography (hexanes:EtOAc-10:1) providing 5.6 g (87%) of the subtitle product.

Provenance & Evidence