Ethyl Acrylate → 3-{2,5-Dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-2-yloxy]-phenyl}-acrylic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

To a degassed solution of [2-(4-bromo-2,5-dichloro-phenoxy)-pyridin-3-yl]-(4-cyclopropyl-3,4-dihydro-2H-quinoxalin-1-yl)-methanone (500 mg, 0.96 mmol, 1.0 equiv; Example 163) in propionitrile (10 mL) under Ar was added N-ethyldiisopropylamine (373 mg, 491 μL, 2.89 mmol, 3.0 equiv; [CAS RN 7087-68-5]), ethyl acrylate (0.58 g, 0.63 mL, 5.78 mmol, 6.0 equiv; [CAS RN 140-88-5]), palladium(II) acetate (22 mg, 0.10 mmol, 0.1 equiv; [CAS RN 3375-31-3]) and tri-o-tolyl-phosphane (59 mg, 0.19 mmol, 0.2 equiv; [CAS RN 6163-58-2]). The reaction mixture was heated to 95° C. over night. The crude reaction was filtered over Celite®, a sat. solution of NaCl (50 mL) added and extracted with ethyl acetate (3×50 mL). The combined organic phases were dried over Na2SO4 and the product purified by silica column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane/ethyl acetate affording 320 mg (62%) of the title compound as a yellow foam. MS (ISN): 538.3 [M+H]+.

Provenance & Evidence