반응 #344529

반응 방정식

sodium nitrite

1-(2-fluoro-4-aminophenyl)-4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-one

→

1-(2-fluoro-4-hydroxyphenyl)-4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-one

수율 60.7%

용매

water

sulfuric acid

sulfuric acid

—

xylenes

water

반응 조건

후처리

1. 1
   온도was maintained between 15° C. and 20° C
2. 2
   온도This two-phase solution was heated
3. 3
   온도at reflux for one hour
4. 4
   온도after which it was cooled
5. 5
   기타the phases separated
6. 6
   건조The organic layer was dried over anhydrous magnesium sulfate
7. 7
   여과filtered
8. 8
   기타The filtrate was evaporated under reduced pressure
9. 9
   기타leaving a brown oil
10. 10
    추출The aqueous layer was extracted with ethyl acetate
11. 11
    건조the extract was dried over anhydrous magnesium sulfate
12. 12
    여과filtered
13. 13
    기타the solvent was evaporated under reduced pressure
14. 14
    기타again leaving a brown oil
15. 15
    세척eluted with methylene chloride/ethyl acetate (90/10)
16. 16
    기타the solvent was evaporated under reduced pressure

실험 절차

A solution of 20.0 g (0.0774 mole) of 1-(2-fluoro-4-aminophenyl)-4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-one in 100 mL of concentrated sulfuric acid was cooled to 15°-20° C. A solution of 5.3 g (0.0774 mole) of sodium nitrite in 20 mL of water was added slowly to the sulfuric acid solution while the temperature was maintained between 15° C. and 20° C. The dark orange solution was stirred for an hour at this temperature. The solution was then added rapidly to a solution of 250 g (1.00 mole) of copper (II) sulfate pentahydrate and 2.0 g (0.0072 mole) of iron (II) sulfate heptahydrate in 250 mL of water and 250 mL of mixed xylenes. This two-phase solution was heated at reflux for one hour, after which it was cooled and the phases separated. The organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure, leaving a brown oil. The aqueous layer was extracted with ethyl acetate, and the extract was dried over anhydrous magnesium sulfate and then filtered. The extract was combined with the brown oil from the organic phase, and the solvent was evaporated under reduced pressure, again leaving a brown oil. This brown oil was placed on a silica gel column and eluted with methylene chloride/ethyl acetate (90/10). The product-containing fractions were combined, and the solvent was evaporated under reduced pressure, leaving 12.17 g of 1-(2-fluoro-4-hydroxyphenyl)-4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-one, m p. 112°-114° C. The NMR spectrum was consistent with the proposed structure.

출처