Hydrochloric Acid → (4R)-4-(4-chloro-3-iodophenyl)pyrrolidin-2-one

Participants

Reaction Steps

To (4R)-4-(3-Amino-4-chlorophenyl)pyrrolidin-2-one (10 g, 47.62 mmol) was added a mixture of 12N HCl (30 mL) and ice cold water (20 mL) and cooled in ice. Sodium nitrite (3.7 g, 52.4 mmol) in 20 mL water was added dropwise. The mixture was stirred for 30 minutes. Potassium iodide (67.5 g, 404.8 mmol) in 100 mL of water was added dropwise at 0° C. The mixture was stirred for 1 h at 0° C. and then for 45 min at room temperature. One-hundred (100) mL of 20% IPA/DCM was added. The organic phase was separated and washed with 10% sodium thiosulfate, followed by water and brine. The combined organic layers were then evaporated in vacuo to give a reddish yellow oil, which was purified by silica gel chromatography (biotage) eluting with methylene chloride/methanol to provide 17.4 g (75% yield) of (4R)-4-(4-chloro-3-iodophenyl)pyrrolidin-2-one.

Provenance & Evidence