Triethylamine → Ethyl 2-(5-bromo-2-fluoronicotinoyl)-3-(dimethylamino)acrylate

Temperature

110 °C

To a solution of 5-bromo-2-fluoronicotinic acid (3 g, 13.64 mmol) in toluene (30 mL) was added thionyl chloride (5 mL, 68.18 mmol, 5 equiv.) followed by DMF (0.5 mL). This was stirred at 110° C. for 2 h then concentrated in vacuo. The residue was resuspended in THF (15 mL) and added dropwise to a solution of ethyl 3-(dimethylamino)acrylate (2 mL, 13.64 mmol) and triethylamine (2.85 mL, 20.45 mmol) in THF (15 mL). The reaction was stirred at 70° C. for 18 h, cooled down to room temperature, and quenched with water. The reaction was partitioned between water (70 mL) and ethyl acetate (70 mL) and the layers were separated. The aqueous layer was extracted with ethyl acetate (2×70 mL). The combined organic layers were washed with 1 N HCl (100 mL) and brine (100 mL), dried over sodium sulftate, and concentrated. The concentrate was purified via silica gel chromotography to provide ethyl 2-(5-bromo-2-fluoronicotinoyl)-3-(dimethylamino)acrylate as an orange solid (3.64 g, 77%).

1. concentrationthen concentrated in vacuo
2. stirringThe reaction was stirred at 70° C. for 18 h
3. temperaturecooled down to room temperature
4. customquenched with water
5. customThe reaction was partitioned between water (70 mL) and ethyl acetate (70 mL)
6. customthe layers were separated
7. extractionThe aqueous layer was extracted with ethyl acetate (2×70 mL)
8. washThe combined organic layers were washed with 1 N HCl (100 mL) and brine (100 mL)
9. dry with materialdried over sodium sulftate
10. concentrationconcentrated
11. customThe concentrate was purified via silica gel chromotography

ORD record

ord-ae425c3860c94e1ba861e1bcc7741587

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08569484B2