4,6-Dichloropyrimidine → 4-Chloro-6-(3,3-difluoropyrrolidin-1-yl)pyrimidine

Participants

Reaction Steps

A solution of 3,3-difluoropyrrolidine (215 mg, 1.5 mmol), 4,6-dichloro-pyrimidine (223 mg, 1.5 mmol) and DIPEA (194 mg, 1.5 mmol) in 1,4-dioxane (3.0 mL) was heated at 100° C. for 16 hours. The reaction was cooled to room temperature and then partitioned between EtOAc and water. The organic phase was separated and washed with saturated sodium chloride solution, dried over sodium sulfate and concentrated. The residue was separated with flash chromatography (25+S Biotage, 20% EtOAc/pentane) to afford 160 mg (48.6%) of 4-chloro-6-(3,3-difluoropyrrolidin-1-yl)pyrimidine as a solid.

Provenance & Evidence