1H-1,2,4-Triazole → HCID 13457296, compound

Temperature

-78 °C

A hexane solution of n-butyllithium (1.55M, 9.6 ml, 14.9 mmole) was added to diethylether (6 ml) and the solution was cooled to -78° C. A solution of 2,4-difluorobromobenzene (3.03 g, 15.7 mmole) in diethylether (100 ml) was added dropwise over 15 minutes and the mixture was stirred at -78° C. for a further 15 minutes. A solution of 1-bromo-3,3,3-trifluoropropan-2-one (2.4 g, 12.6 mmole) in diethylether (100 ml) was then added dropwise over 15 minutes and the mixture was stirred at -78° C. for a further 30 minutes. A solution of glacial acetic acid (2 ml) in diethylether (5 ml) was then added, followed by water (15 ml) and the mixture was allowed to warm to 0° C. The aqueous layer was separated and washed with diethylether (2×30 ml). The combined diethylether extracts were dried over magnesium sulphate, evaporated, and the residual oil was dissolved in dimethylformamide (40 ml). 1,2,4-Triazole (2.5 g, 36.2 mmole) and anhydrous potassium carbonate (10 g, 72.5 mmole) were then added to this solution and the mixture was stirred and heated at 70° C. for 18 hours. The mixture was then cooled, poured into water (150 ml) and extracted with ethyl acetate (3×100 ml). The combined ethyl acetate extracts were washed with water (100 ml), dried over magnesium sulphate, and evaporated. The residue was chromatographed on silica (230-400 mesh), eluting with ethyl acetate:hexane, 60:40 by volume, to give, after one recrystallization from ethyl acetate/hexane, the title compound, 1.7 g (47%), m.p. 110°-111° C.

1. stirringthe mixture was stirred at -78° C. for a further 30 minutes
2. temperatureto warm to 0° C
3. customThe aqueous layer was separated
4. washwashed with diethylether (2×30 ml)
5. dry with materialThe combined diethylether extracts were dried over magnesium sulphate
6. customevaporated
7. dissolutionthe residual oil was dissolved in dimethylformamide (40 ml)
8. stirringthe mixture was stirred
9. temperatureheated at 70° C. for 18 hours
10. temperatureThe mixture was then cooled
11. extractionextracted with ethyl acetate (3×100 ml)
12. washThe combined ethyl acetate extracts were washed with water (100 ml)
13. dry with materialdried over magnesium sulphate
14. customevaporated
15. customThe residue was chromatographed on silica (230-400 mesh)
16. washeluting with ethyl acetate
17. customhexane, 60:40 by volume, to give
18. customafter one recrystallization from ethyl acetate/hexane

ORD record

ord-efafc8d8b0944fb182fbb72cdd59a3bc

Source dataset

uspto-grants-1985_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04518604