Hydrochloric Acid → HCID 66643896, compound

Participants

Reaction Conditions

Reaction Steps

To a flask charged with 2-bromo-1-(bromomethyl)-3-fluorobenzene (2.0 g, 7.5 mmol) and a stir bar was added dimethyl malonate (20.0 mL, 174 mmol). The solution was cooled to 0° C. in an ice bath. To this solution was carefully added sodium hydride (0.597 g, 14.9 mmol) in small portions. When the addition was done, the reaction was kept stirring for another 30 minutes. The reaction was quenched with NH4Cl, extracted with EtOAc, washed with brine, dried over Na2SO4, and concentrated. The residue was dissolved in acetic acid (50 mL). To this solution was added HCl (50 ml, 330 mmol), and the reaction was heated to reflux for 16 hours. Analysis by LC showed formation of the desired acid. Most of the solvent was removed on a rotary evaporator. The remaining solution was diluted with 50 mL of water, and extracted with ether (50 mL×3). The extracts were combined, and washed with 1N NaOH (50 mL×2). At that point, all the acid was in the aqueous as the salt. The aqueous washes were combined, acidified, and back extracted with DCM (100 mL×2). The extracts were combined, dried over Na2SO4, and concentrated to afford 3-(2-bromo-3-fluorophenyl)propanoic acid.

Provenance & Evidence