Potassium Carbonate → (2R,3S)-2-(3-Chloro-4-cyano-2-propylphenylamino)-3-hydroxybutanoic acid

Participants

Reaction Conditions

Reaction Steps

2-Chloro-4-fluoro-3-propylbenzonitrile (CAS 924626-89-1, 3.22 g, 16.3 mmol) was mixed together with H-D-Thr-OH (2.33 g, 19.6 mmol) in DMSO (30 mL) at room temperature. K2CO3 (4.73 g, 34.2 mmol) was added and the reaction mixture was stirred at 80° C. for 40 h. The reaction mixture was then cooled to room temperature and partitioned between water and EtOAc. The layers were separated and the aqueous extract was washed once with EtOAc. The aqueous extract was then acidified by slow addition of citric acid and stirred for 10 min at room temperature. The solution was extracted with EtOAc several times and the organic extracts were combined, washed with water, dried over Na2SO4, filtered, and concentrated in vacuo to obtain the crude product (0.650 g, 13% yield), which was carried on to the next step without further purification.

Provenance & Evidence