Triethylamine → (Z)-ethyl 3-(dimethylamino)-2-(2-fluoro-5-iodobenzoyl)acrylate

2-Fluoro-5-iodobenzoic acid (5.20 g, 19.55 mmol, Aldrich) was suspended in thionyl chloride (1.427 mL, 19.55 mmol, Aldrich) and heated to reflux for 30 min The reaction mixture was cooled to room temperature and concentrated under reduced pressure to a tan solid. The solid was dissolved in toluene (30 mL) and concentrated under reduced pressure again. To a solution of the resulting solid (5.20 g, 19.55 mmol) in toluene (30 mL) was added triethylamine(2.72 mL, 19.55 mmol, Acros) and (Z)-ethyl 3-(dimethylamino)acrylate (3.64 mL, 25.41 mmol, Acros) and the reaction mixture was heated to 90° C. for 1 h. The reaction mixture was diluted with water and extracted three times with ethyl acetate. The combined organic extracts were dried over magnesium sulfate, filtered and concentrated under reduced pressure. Purification by Isco column (0%-100% ethyl acetate/dichloromethane) afforded the desired compound as a yellow solid (6.51 g).

1. temperatureheated
2. temperatureto reflux for 30 min The reaction mixture
3. concentrationconcentrated under reduced pressure to a tan solid
4. dissolutionThe solid was dissolved in toluene (30 mL)
5. concentrationconcentrated under reduced pressure again
6. temperaturethe reaction mixture was heated to 90° C. for 1 h
7. extractionextracted three times with ethyl acetate
8. dry with materialThe combined organic extracts were dried over magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customPurification by Isco column (0%-100% ethyl acetate/dichloromethane)

ORD record

ord-b22ead0afa464e24b53fb16591dcfa3d

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08283361B2