2,6-Dibromopyridine → 4-(6-Bromo-2-pyridinyl)morpholin-3-one

関与物質

反応条件

反応手順

**_September 10 2015_** morpholin-3-one (1g, 9.89 mmol), 2,6-dibromopyridine (3.51 g, 14.84 mmol), PdOAc2 (0.222 g, 0.99 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (1.145 g, 1.98 mmol) and CS2CO3 (6.12 g, 18.79 mmol) in 1,4-dioxane (20 mL) were heated at 80 °C for 12 hours. **_September 11 2015_** LCMS showed no precursor and 37% of the desired mass MH+ 257/259 @ 0.86 min along with lots of unknowns on a 2-min basic run. The reaction was cooled to RT, and filtered off the solid (Cs2CO3). The filter was concentrated, re-dissolved in EtOAc, washed with waster, dried through MgSO4, and evaporated to give an orange gum. **_September 14 2015_** The orange gum was added to a Biotage column and was eluted with 10-100%EtOAc in Heptane. Collected fractions. The column was stuck as 37% EtOAc in Heptane. A lot of CH2Cl2 was pushed through the column manually, and then continued the elution with 0-100% EtOAc in DCM. Collected fractions. The product fractions were identified, combined based on LCMS and TLC, and evaporated to give a white solid as the desired product (EN07946-27-001). Based on LCMS, it was 98% pure; based on NMR in DMSO, it was > 95%pure; _however, based on NMR in CDCl3, there were ~30% impurity in the aromatic proton region._ The product was used for next step without further purification.

情報源と証拠