2-Bromopropionic acid → (E)-2-Methyl-3-(4-phenyl-thiophen-2-yl)-acrylic acid

A 50 ml round bottomed flask was charged with diethylphosphite (684 μl, 5.31 mmol) and treated sequentially with sodium hydride (637 mg, 15.94 mmol, 60% in mineral oil) in DME (20 ml), followed by 2-bromopropionic acid (478 μl, 5.31 mmol). The reaction was stirred at room temperature until hydrogen evolution ceased. Next 4-phenyl-2-thiophenecarboxaldehyde (1.0 g, 5.31 mmol) was added and the reaction stirred for 1 h. The reaction was quenched by the addition of EtOH (5 ml) and the contents of the flask poured into distilled water (20 ml). The strongly basic solution was washed with diethyl ether (25 ml) to remove traces of mineral oil, the aqueous layer acidified to pH 4 with concentrated HCl and extracted with diethyl ether (2×25 ml). The organic layer was dried (MgSO4) and the solvent removed in vacuo. The crude residue was washed with petroleum spirit 40-60° C., and the resulting insoluble solid, fractionally crystallized from dichloromethane to afford the title compound as a white solid (335.2 mg, 29%).

1. customThe reaction was quenched by the addition of EtOH (5 ml)
2. additionthe contents of the flask poured
3. distillationinto distilled water (20 ml)
4. washThe strongly basic solution was washed with diethyl ether (25 ml)
5. customto remove traces of mineral oil
6. extractionextracted with diethyl ether (2×25 ml)
7. dry with materialThe organic layer was dried (MgSO4)
8. customthe solvent removed in vacuo
9. washThe crude residue was washed with petroleum spirit 40-60° C.
10. customthe resulting insoluble solid, fractionally crystallized from dichloromethane

ORD record

ord-b83f72bfdee2459c90cdb5ed51f9e915

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09216992B2