1H-1,2,4-Triazole → 2-(2,4-Difluorophenyl)-3,3,4,4,4-pentafluoro-1-(1H-1,2,4-triazol-1-yl)-butan-2-ol

Temperature

-78 °C

n-Butyl lithium (3.32 ml of a 1.5 molar solution in hexane; 0.00498 mole) in diethylether (5 ml) was cooled and stirred at -78° C. A solution of 2,4-difluorobromobenzene (1.0 g; 0.00519 mole) in ether (8 ml) was added slowly over 15 minutes. The reaction mixture was held for 15 minutes at -78° C. 1-Bromo-3,3,4,4,4-pentafluorobutanone (1.0 g; 0.00415 mole) in 6 ml of ether was then added over 15 minutes at -78° C. The mixture was stirred for 30 minutes at -78° C. Acetic acid (0.7 g) in ether (5 ml) was added followed by water (8 ml), and the mixture was allowed to warm to room temperature. The ether layer was separated and the aqueous layer was washed with 2×15 ml of ether. The combined ether layers were dried over magnesium sulphate and evaporated to give an oil. To this oil were added 1,2,4-triazole (0.86 g; 0.01245 mole); anhydrous potassium carbonate (5.73 g; 0.0415 mole) and anhydrous dimethylformamide (15 ml). The mixture was heated and stirred at 80° C. for 3.5 hours, cooled to room temperature and poured into 150 ml of water. The mixture was then extracted with 3×60 ml methylene chloride, and the combined organic extracts were dried over magnesium sulphate, evaporated and then co-distilled with xylene. The residual brown oil was chromatographed on silica (230-400 mesh) under pressure. Elution with a mixture of ethyl acetate/hexane (60/40 by volume) gave the title compound as a white solid (400 mgs; 28%), melting point 95°-6° C. after crystallization from cyclohexane.

1. stirringThe mixture was stirred for 30 minutes at -78° C
2. temperatureto warm to room temperature
3. customThe ether layer was separated
4. washthe aqueous layer was washed with 2×15 ml of ether
5. dry with materialThe combined ether layers were dried over magnesium sulphate
6. customevaporated
7. customto give an oil
8. temperatureThe mixture was heated
9. stirringstirred at 80° C. for 3.5 hours
10. temperaturecooled to room temperature
11. extractionThe mixture was then extracted with 3×60 ml methylene chloride
12. dry with materialthe combined organic extracts were dried over magnesium sulphate
13. customevaporated
14. customThe residual brown oil was chromatographed on silica (230-400 mesh) under pressure
15. washElution
16. additionwith a mixture of ethyl acetate/hexane (60/40 by volume)

ORD record

ord-b3ce3e92a22a41ea8e6391749a9e525e

Source dataset

uspto-grants-1986_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04616027