Propanamide, N,N-dimethyl- → 1-(5-(4-chlorophenyl)-1-ethyl-4-methyl-1H-pyrrol-2-yl)propan-1-one

Temperature

25 °C

Phosphorus oxychloride (0.47 g, 0.28 ml, 3.00 mmol) was added dropwise to previously cooled (0 to 5° C.) N,N-dimethyl propionamide (0.30 g, 0.27 ml, 3.00 mmol) maintaining the temperature between about 0° C. to about 5° C. The resulting reaction mixture was then allowed to warm to room temperature (about 25° C.), which was then stirred at room temperature (about 25° C.) for 20 minutes. The reaction mixture was then diluted with 1,2-dichloroethane (15 ml), the resulting mixture was cooled to 0° C., to it was then added 2-(4-chlorophenyl)-1-ethyl-3-methyl-1H-pyrrole (compound 51a, 0.6 g, 2.73 mmol) in 1,2-dichloroethane (15 ml) dropwise. The reaction mixture so formed was heated to reflux for 30 minutes. The progress of the reaction was monitored by TLC. The reaction mixture was then allowed to cool to room temperature, and to it was then added a solution of sodium acetate trihydrate (1.23 g, 15.0 mmol) in 14 ml water. The reaction mixture so obtained was heated to reflux for 30 minutes. Two phases formed in the reaction mixture were then separated. The aqueous layer was extracted with dichloromethane (3×30 ml). The combined organic layer was washed with water (1×30 ml) and dried over anhydrous Na2SO4. The solvent was evaporated from the dried organic layer under reduced pressure to obtain a crude product, which was then purified by flash column chromatography using 10% ethyl acetate in hexanes as an eluent to obtain the title compound (0.5 g, 66.4%).

1. temperaturemaintaining the temperature between about 0° C. to about 5° C
2. customThe resulting reaction mixture
3. temperaturethe resulting mixture was cooled to 0° C., to it
4. customThe reaction mixture so formed
5. temperaturewas heated
6. temperatureto reflux for 30 minutes
7. temperatureto cool to room temperature
8. customThe reaction mixture so obtained
9. temperaturewas heated
10. temperatureto reflux for 30 minutes
11. customTwo phases formed in the reaction mixture
12. customwere then separated
13. extractionThe aqueous layer was extracted with dichloromethane (3×30 ml)
14. washThe combined organic layer was washed with water (1×30 ml)
15. dry with materialdried over anhydrous Na2SO4
16. customThe solvent was evaporated from the dried organic layer under reduced pressure
17. customto obtain a crude product, which
18. customwas then purified by flash column chromatography

ORD record

ord-589fd1076ded4336b59ef6101cad070e

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09393247B2