Acetic Acid → Ethyl (R)-(+)-4-bromo-3-hydroxybutyrate

Participants

Reaction Steps

To a 50 mL round bottom flask equipped with a magnetic stirring bar and nitrogen (N2) inlet was charged 2.13 g (S)-3-hydroxybutyrolactone (Example 2) (95.7% pure by VPC) and 5.0 mL acetic acid. The flask was cooled using an ice bath and 9.0 mL of 33% hydrogen bromide (HBr) in acetic acid was charged dropwise over several minutes upon which the ice bath was removed and the mixture allowed to warm to room temperature and stirred overnight under N2. An additional 1.0 mL of 33% HBr in acetic acid was added when VPC indicated that the reaction was not complete, and the mixture was stirred overnight at room temperature. The reaction was quenched by pouring into ethyl alcohol (85 mL) and heated at reflux until the reaction was complete (8 hours). The solvent was removed and the residue taken up in ethyl acetate (100 mL), washed with dilute aqueous sodium bicarbonate (NaHCO3) solution (25 mL), water (25 mL), and brine (25 mL). The organic layer was distilled and the residue purified by silica gel chromatography to yield 1.74 g (41.5%) of the title compound.

Provenance & Evidence