Citric Acid → N-[4-(4-Fluoro-2-methoxy-phenyl)-6-methyl-pyridin-3-yl]-3-methanesulfonyl-N-methyl-5-trifluoromethyl-benzamide

Participants

Reaction Conditions

Reaction Steps

To a solution of N-(6-chloro-4-(4-fluoro-2-methoxyphenyl)pyridin-3-yl)-N-methyl-3-(methylsulfonyl)-5-(trifluoromethyl)benzamide (0.1 g, 0.193 mmol, example 201) in THF (2 mL) were added methylzinc chloride (0.145 mL, 0.29 mmol, 2M solution in THF, CAS RN 5158-46-3), 1,3-dimethyl-2-imidazolidinone (0.4 mL, CAS RN 80-73-9) and (1,3-bis(2,6-diisopropyl-phenyl)imidazolidene) (3-chloropyridyl) palladium(II) dichloride (PEPPSI-IPr, 2.63 mg, 3.87 μmol, Aldrich). The reaction mixture was stirred at 50° C. for 30 min. and then poured on 10% aqueous citric acid solution and EtOAc and the layers were separated. The aqueous layer was extracted twice with EtOAc. The organic layers were washed with brine, dried over MgSO4, filtered, treated with silica gel and evaporated. The compound was purified by silica gel chromatography on a 10 g column using a MPLC system eluting with a gradient of n-heptane:EtOAc (100:0 to 0:100), followed by a second chromatography, using preparative HPLC (Gemini NX column) eluting with a gradient of methanol:water (containing 0.1% formic acid) (20:80 to 98:2). Colorless solid (0.073 g; 76%). MS (ESI): m/z=497.11 [M+H]+.

Provenance & Evidence