1,3-Dichloroacetone → 4-(hydroxymethyl)-2-[(E)-2-[4-(trifluoromethyl)phenyl]ethenyl]-1,3-oxazole

Temperatur

72.5 °C

(E)-3-(4-(Trifluoromethyl)phenyl)-2-propenamide (20.0 g, 92.9 mmol) was added to toluene (75 ml), and 1,3-dichloroacetone (22.0 g, 173.3 mmol) and toluene (25 ml) were added. The mixture was subjected to refluxing azeotropic dehydration for 9 hours. The reaction mixture was divided into two equal portions and one of them was concentrated under reduced pressure. To the residue were added dimethyl sulfoxide (100 ml), sodium acetate trihydrate (15.9 g, 116.8 mmol) and water (20 ml). The mixture was stirred at 70-75° C. for 4.5 hours. 2N-Aqueous sodium hydroxide solution (60 ml) was added at the same temperature and the mixture was stirred for 1 hour. After allowing to cool to room temperature, toluene (400 ml) and water (400 ml) were added and the mixture was partitioned. After washing with 5% brine (200 ml), the organic layer was concentrated under reduced pressure. To the residue was added methanol (10 ml) and the mixture was heated to 60° C. to allow dissolution. After allowing to cool to room temperature and stirring, the mixture was stirred for 1 hour under ice-cooling. The precipitated crystals were collected by filtration, washed with cold-methanol (5 ml) and dried under reduced pressure to give 4-(hydroxymethyl)-2-[(E)-2-[4-(trifluoromethyl)phenyl]-ethenyl]-1,3-oxazole (5.96 g, 22.1 mmol, yield 48%).

1. additionwere added
2. temperatureto refluxing azeotropic dehydration for 9 hours
3. concentrationwas concentrated under reduced pressure
4. stirringthe mixture was stirred for 1 hour
5. temperatureto cool to room temperature
6. customthe mixture was partitioned
7. washAfter washing with 5% brine (200 ml)
8. concentrationthe organic layer was concentrated under reduced pressure
9. additionTo the residue was added methanol (10 ml)
10. temperaturethe mixture was heated to 60° C.
11. dissolutiondissolution
12. temperatureto cool to room temperature
13. stirringstirring
14. stirringthe mixture was stirred for 1 hour under ice-
15. temperaturecooling
16. filtrationThe precipitated crystals were collected by filtration
17. washwashed with cold-methanol (5 ml)
18. customdried under reduced pressure

ORD-Eintrag

ord-53d8c61a726a49a69c1f9999860c037c

Quelldatensatz

uspto-grants-2004_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06743924B2