Dicyclohexylamine → (S)-2-(Acetylthio)-4-methylpentanoic acid

Participants

Reaction Conditions

Reaction Steps

Thioacetic acid (13.7 g, 180 mmol) and DMF (300 mL, 4 mol) were combined, and the mixture cooled in an ice bath. Sodium carbonate (19.0 g, 180 mmol) was added. After 30 minutes, (R)-2-bromo-4-methylpentanoic acid (33.4 g, 171 mmol) in DMF (20 mL) was added dropwise and the mixture was stirred at 0° C. to room temperature over 7 hours. The reaction was diluted with EtOAc (200 mL) and washed with a 1:1 saturated aqueous NaCl:1N HCl solution (200 mL). The layers were separated and the aqueous phase was extracted again with EtOAc (200 mL). The organics were combined, washed with saturated aqueous NaCl, dried over MgSO4, filtered, and concentrated under reduced pressure. The recovered oil was dissolved into diisopropyl ether (150 mL, 1.1 mol) and chilled at 0° C. Dicyclohexylamine (33.4 mL, 168 mmol) was added dropwise and the solid was allowed to precipitate out of solution. After stirring for an additional 30 minutes the material was filtered and washed with cold diisopropyl ether (150 mL). The recovered solid (41 g) was suspended in EtOAc (300 mL), 5% KHSO4 (500 mL) was added, and the layers were separated. The organic was washed with saturated aqueous NaCl, dried over MgSO4, filtered, and concentrated under reduced pressure. The recovered oil was then azeotroped with toluene (3×50 mL) to yield the title compound as a yellow oil (20.7 g).

Provenance & Evidence