Sodium Carbonate → (S)-3-(4-(5-Chloropyridazin-3-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one

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Reaction Steps

To a 0.5-2.0 mL microwave vial charged with (S)-5,5-dimethyl-4-phenyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)oxazolidin-2-one (Intermediate J) (0.240 g, 0.610 mmol) and 3,5-dichloropyridazine (commercially available from ACES Pharma, Princeton, N.J.) (0.100 g, 0.671 mmol) were added dioxane (1.220 mL), and 2 M Na2CO3 (1.220 mL). Nitrogen was bubbled through the resulting suspension and then Pd(PPh3)4 (0.071 g, 0.061 mmol) was added. The resulting mixture was irradiated at 100° C. for 30 minutes. LC-MS indicated the formation of product as a major species (two close peaks with product mass, likely isomers) along with other impurities with consumption of starting material. The dark suspension was diluted with water, transferred to a separatory funnel, and extracted with EtOAc (2×). The combined organic layers were dried with Na2SO4, filtered, and dried under reduced pressure. The residual material was purified with a 40 g HP 15 μm spherical silica column (Interchim) ramping EtOAc in heptane from 0-100% leading to isolation of product (primarily one isomer) as the major species with 10-15% impurity. (S)-3-(4-(5-Chloropyridazin-3-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one (0.058 g, 0.153 mmol, 25.02% yield) was obtained as a white solid. Note: the regiochemistry of the product was not confirmed, but it was assumed that the major product would result from the more reactive chloride). m/z (ESI) 380.1 (M+H)+.

Provenance & Evidence