Cesium carbonate → N-(4-(4-chloro-2-fluoro-3-methoxyphenyl)-5-formylpyridin-2-yl)acetamide

Temperature

85 °C

A stirred solution of N-(4-chloro-5-formylpyridin-2-yl)acetamide (1.947 g, 8.72 mmol) (prepared as described in Example 18, Part D), 2-(4-chloro-2-fluoro-3-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2.5 g, 8.72 mmol), cesium carbonate (5.69 g, 17.45 mmol) and Pd(PPh3)4 (0.504 g, 0.436 mmol) in a mixture of dioxane (30 mL) and water (5 mL) was purged with nitrogen for 5 minutes then heated to 85° C. for 14 h. The reaction mixture was cooled to rt and diluted with water (10 mL). The mixture was extracted with ethyl acetate (2×15 mL). The combined organic layers were washed with brine (20 mL), dried over sodium sulphate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography using a gradient of ethyl acetate in hexanes to yield N-(4-(4-chloro-2-fluoro-3-methoxyphenyl)-5-formylpyridin-2-yl)acetamide (1.78 g, 2.95 mmol, 34% yield) as a white solid. LCMS (ESI) m/e 322.9 [(M+H)+, calcd for C15H13ClFN2O3 323.1]; LC/MS retention time (Method F): tR=0.89 min.

1. customwas purged with nitrogen for 5 minutes
2. temperatureThe reaction mixture was cooled to rt
3. additiondiluted with water (10 mL)
4. extractionThe mixture was extracted with ethyl acetate (2×15 mL)
5. washThe combined organic layers were washed with brine (20 mL)
6. dry with materialdried over sodium sulphate
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified by silica gel chromatography

ORD record

ord-eaa14a6912694ae6bbf93c00516a3c42

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08703953B2