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

Temperature

25 °C

Phosphorus oxychloride (1.496 g, 0.896 ml, 9.76 mmol) was added dropwise to previously cooled (0 to 5° C.) N,N-dimethyl propionamide (0.987 g, 1.073 ml, 9.76 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 15 minutes. The reaction mixture was then diluted with 1,2-dichloroethane (17 ml), the resulting mixture was cooled to 0° C., to it was then added 2-(4-chlorophenyl)-3-methyl-1H-pyrrole (prepared according to the procedure given in Tetrahedron Letters 46 (2005) 4539-4542, 1.7 g, 8.87 mmol) in 1,2-dichloroethane (17 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 (6.64 g, 48.8 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 (3×50 ml). The combined organic layer was washed with saturated sodium bicarbonate solution (1×50 ml) followed by washing with water (1×50 ml), and then the organic layer was dried over anhydrous Na2SO4. The solvent was evaporated from the dried organic layer under reduced pressure to obtain a crude product. The crude product was then purified by flash column chromatography using 10% ethyl acetate in hexanes as an eluent to obtain the title compound (1.82 g, 83%)

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 (3×50 ml)
14. washThe combined organic layer was washed with saturated sodium bicarbonate solution (1×50 ml)
15. washby washing with water (1×50 ml)
16. dry with materialthe organic layer was dried over anhydrous Na2SO4
17. customThe solvent was evaporated from the dried organic layer under reduced pressure
18. customto obtain a crude product
19. customThe crude product was then purified by flash column chromatography

ORD record

ord-0a1c838a9e0042b58acb9d2155425f76

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09393247B2