4-(3,3-Difluoropyrrolidin-1-yl)piperidine → Methyl 3-{[4-(3,3-difluoro-1-pyrrolidinyl)-1-piperidinyl]methyl}-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

Participants

Reaction Steps

To a suspension of methyl 3-(bromomethyl)-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1.05 g, 2.090 mmol) in acetonitrile (13.94 mL) was added 4-(3,3-difluoro-1-pyrrolidinyl)piperidine (0.517 g, 2.72 mmol). After 15 h, additional 4-(3,3-difluoro-1-pyrrolidinyl)piperidine (0.188 g, 0.988 mmol, 0.47 equiv.) was added. The mixture was stirred at room temperature for 4 days. The solvent was removed, and the residue was absorbed onto florisil and purified via column chromatography (ISCO 0.5-3% methanol/methylene chloride) to give methyl 3-{[4-(3,3-difluoro-1-pyrrolidinyl)-1-piperidinyl]methyl}-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (0.976 g, 73% yield) as a yellow foam. MS (m/z) 612.2 (M+H+).

Provenance & Evidence