2-Chloro-5-(trifluoromethyl)pyridine → Ethyl 2-[[5-(trifluoromethyl)-2-pyridinyl]amino]-1,3-oxazole-5-carboxylate

Participants

Reaction Conditions

Reaction Steps

Objective: Test of scope in the coupling of ester substituted aminooxazole To an oven-dried microwave vial was added ethyl 2-aminooxazole-5-carboxylate (156 mg, 1.00 mmol), 2-chloro-5-(trifluoromethyl)pyridine (181 mg, 1.00 mmol), cesium carbonate (651 mg, 2.00 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (22.87 mg, 0.02 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (43.4 mg, 0.075 mmol) and the vial was capped and purged with nitrogen. dioxane (4 mL) (degassed) was added and the reaction mixture was heated to 160 °C for 1 h under microwave irradiation. LCMS of the crude reaction mixture indicated that the desired product had been formed with very small amounts of side products apparent. DCM (20 mL) was added to the crude reaction mixture together with silica (2 g) and the solvent was removed from the reaction mixture under reduced pressure. The resulting residue was then placed in a dry-load tube prior to chromatography. The crude product was purified by flash silica chromatography, elution gradient 0 to 5% methanolic ammonia in DCM. Pure fractions were evaporated to dryness to afford the desired product in 74% yield and 92% purity by LCMS. The product was triturated with MeCN to give a solid which was collected by filtration and dried under vacuum to give ethyl 2-(5-(trifluoromethyl)pyridin-2-ylamino)oxazole-5-carboxylate (185 mg, 61.5 %) as a cream solid. This material was shown to be > 95% pure based on proton NMR strength. Conclusion: The desired product was formed in moderate yield and high purity.

Provenance & Evidence