Phosphorus oxychloride → 1-(4-bromo-phenyl)-6-chloro-3-cyclopropyl-1H-pyrimidine-2,4-dione

To 1-(4-bromo-phenyl)-3-cyclopropyl-pyrimidine-2,4,6-trione 32 (11.8 g) obtained in Step 2 was added water (1.31 ml) and phosphorus oxychloride (17.0 ml) was added dropwise with stirring at room temperature. After the completion of the dropwise addition, the mixture was stirred at 110° C. for 3 hrs. After allowing to cool to room temperature, the reaction mixture was added to ice water by small portions and the mixture was stirred. The mixture was stirred at room temperature and extracted with chloroform. The organic layer was washed with brine, and dried over anhydrous magnesium sulfate. Anhydrous magnesium sulfate was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography (hexane:ethyl acetate=2:1→chloroform:acetone=30:1) to give a 1:1.4 mixture (11.6 g, yield 93%) of 1-(4-bromo-phenyl)-6-chloro-3-cyclopropyl-1H-pyrimidine-2,4-dione 33 and 3-(4-bromo-phenyl)-6-chloro-1-cyclopropyl-1H-pyrimidine-2,4,-dione 34 as a pale-yellow foamy oil.

1. additionwas added dropwise
2. additionAfter the completion of the dropwise addition
3. stirringthe mixture was stirred at 110° C. for 3 hrs
4. temperatureto cool to room temperature
5. stirringthe mixture was stirred
6. stirringThe mixture was stirred at room temperature
7. extractionextracted with chloroform
8. washThe organic layer was washed with brine
9. dry with materialdried over anhydrous magnesium sulfate
10. filtrationAnhydrous magnesium sulfate was filtered off
11. concentrationthe filtrate was concentrated under reduced pressure
12. customThe residue was purified by column chromatography (hexane:ethyl acetate=2:1→chloroform:acetone=30:1)

ORD-Eintrag

ord-d242cace357a4bf19ab0473faeb68f57

Quelldatensatz

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08835443B2