Reaktion #442
ord-ea8e215424fc4a3cbe2138b915565d9a
Reaktionsgleichung
Lösungsmittel
Reaktionsbedingungen
Vorschrift
Objective: Repeat of optimised conditions found in process research and devellopment screen for an isolated yield. An activated catalyst solution was prepared by adding TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (61.3 mg, 0.07 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (77 mg, 0.13 mmol) to an oven-dried microwave vial. The vial was then capped, purged with nitrogen and anisole (1 mL) (degassed) was added. The solution was stirred at 50°C for 40 mins, then 90°C for 15 mins (activated catalyst solution, Soln. 1). To another oven-dried microwave vial was added potassium carbonate (126 mg, 0.91 mmol), ethyl 2-aminooxazole-5-carboxylate (190 mg, 1.22 mmol) and 2,4-dichloropyridine (90 mg, 0.61 mmol) and the vial was capped and purged with nitrogen. anisole (1.6 mL) and the activated catalyst solution (0.45 mL of Soln. 1 from above) were added (this corresponds to a catalyst loading of 10% Pd). The vessel was then heated to 120°C for 16 h. LCMS and TLC of the crude reaction mixture showed none of the desired product to be present. Some of the amine starting material appears to be present and none of the 2,4-dichloropyridine remains. The mass for the double addition product (addition at the 2- and 4-positions) is present, but co-elutes with the reaction solvent anisole and is not quantifiable as a result. Conclusion: This is a somewhat surprising result, based on the fact that the previous reaction (EN05378-17) results in the formation of significant coupled product. These reaction conditions are apparently not suitable for the coupling of the ester substituted 2-aminooxazole.