2,4-Dichloropyridine → Ethyl 2-[(4-chloro-2-pyridinyl)amino]-1,3-oxazole-5-carboxylate

Participants

Reaction Conditions

Reaction Steps

Objective: Series of experiments to optimise yield of the above coupled product. Pd2(dba)3 (22.89 mg, 0.025 mmol), bis(3,5-bis(trifluoromethyl)phenyl)(2',4',6'-triisopropyl-3,6-dimethoxybiphenyl-2-yl)phosphine (80 mg, 0.10 mmol), 2,4-dichloropyridine (148 mg, 1.00 mmol), cesium carbonate (651 mg, 2.00 mmol),ethyl 2-aminooxazole-5-carboxylate (156 mg, 1.00 mmol) and 4,4'-di-tert-butylbiphenyl (60 mg, 0.23 mmol) were added to an oven dried microwave vial, the vial was capped and placed under an inert atmosphere, dioxane (4 mL) was added and the resulting mixture was heated at 160 °C for 1 h by microwave irradiation under a nitrogen atmosphere. Crude LCMS shows a switch in regioselectivity again with respect to the bidentate ligand Xantphos, with the other isomer becoming the major product in 28% yield based on internal standard (note: this is a rough estimate as the U.V absorbance may be significantly different to the other regioisomer). None of the other regioisomer observed. Conclusion: Switch in regioselectivty with the change in ligand may be worth pursuing, this reaction is _apparently_ completely selective for the 4-regioisomer. Note: Necessary to isolate product to confirm.

Provenance & Evidence