Potassium Phosphate, Tribasic → [3-chloro-6-(2,2-difluoro-2-phenyl-ethylamino)-pyridin-2-yl]-acetic Acid Ethyl Ester

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Reaction Conditions

Reaction Steps

A mixture of (3,6-dichloro-pyridin-2-yl)-acetic acid ethyl ester (139 mg, 593 μmol), as prepared in the previous step, 2,2-difluoro-2-phenylethylamine (132.5 mg, 844 μmol) (see Example 8a), K3PO4 (317 mg, 1.50 mmol) (Fluka, Catalog # 04347), Pd(OAc)2 (5.8 mg, 26 μmol), biphenyl-2-yl-dicyclohexyl-phosphane (22 mg, 62 μmol) (Strem) was taken up in dry, argon-sparged dioxane (650 μL), and the mixture was sealed under a blanket of argon. The yellowish heterogeneous mixture was microwaved with stirring (Smith Synthesizer) at 150° C. for 20 min, and the resulting amber-red heterogeneous mixture was diluted with 8 mL ether, filtered, and concentrated. Flash silica chromatography of the residue (6:1 hexanes/EtOAc eluent) afforded the title compound as a light yellow oil (128 mg, 61%).

Provenance & Evidence