Hydrochloric Acid → Hydrochloric Acid

Participants

Reaction Steps

(R)-3-(S)-hydroxyphenylmethyl)pyrrolidine-1-carboxylic acid t-butyl ester (2.0 g, 7.2 mmol) was dissolved in anhydrous DMF (10 mL, 100 mmol). Lithium hydride (86 mg, 11 mmol) was added in 3 separate portions. The mixture was stirred at room temperature for 15 minutes. Into the mixture was added 3,5-dichlorofluorobenzene (1.7 mL, 14 mmol), and the resultant mixture stirred at room temperature for 15 minutes. The mixture was then stirred at 70° C. overnight. The mixture was cooled to room temperature, and EtOAc (80 mL) and 1M HCl (50 mL) were added. After mixing, the phases were separated and the organic layer was washed with diluted aqueous NaCl (1×50 mL), dried over Na2SO4, and concentrated to dryness to yield 3.5 g of crude product. Into the crude product was added 25 mL cold HCl in an EtOH/EtOAc solution and stirred at room temperature for 3 hours. Most of the solvent was removed by rotary evaporation, EtOAc was added (50 mL) and most of the solvent was removed again. Recrystallization and reslurry from EtOAc (20 mL) gave (R)-3-[(S)-(3,5-dichlorophenoxy)phenylmethyl]pyrrolidine as an HCl salt (2 g, ˜99% purity).

Provenance & Evidence