Acetyl chloride → 1-[5-(4-Fluoro-phenyl)-3-methyl-3H-[1,2,3]-triazol-4-yl]-ethanone

Temperature

-35 °C

To a suspension of 4-(4-fluoro-phenyl)-1-methyl-1H-[1,2,3]triazole (3.54 g, 20.0 mmol) in DME (52 mL) was added n-BuLi (1.6 M in hexane, 15.0 mL, 24.0 mmol) dropwise at −75° C. The mixture was allowed to warm up to −35° C. and was stirred at −35° C. for 1 h. The reaction mixture was cooled again to −78° C. and a light green suspension of CuCN (1.79 g, 20.0 mmol) and LiCl (1.70 g, 40.0 mmol) in THF (26 ml) was added rapidly while stirring at −78° C. After 1 h the mixture was allowed to warm up to −35° C. and acetyl chloride (7.10 mL, 100.0 mmol) was added dropwise at this temperature. Then the reaction mixture was stirred at room temperature for 2 h and then poured carefully into aqueous saturated sodium carbonate solution (150 mL) and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over sodium sulphate, filtered and evaporated. Purification by chromatography (silica, 0 to 100% ethyl acetate in heptane) afforded the title compound (2.2 g, 50%) as a yellow oil. MS: m/e=220.3 [M+H]+.

1. temperatureThe reaction mixture was cooled again to −78° C.
2. additionwas added rapidly
3. stirringwhile stirring at −78° C
4. waitAfter 1 h the mixture was allowed
5. temperatureto warm up to −35° C.
6. stirringThen the reaction mixture was stirred at room temperature for 2 h
7. extractionextracted with ethyl acetate
8. washThe combined organic extracts were washed with brine
9. dry with materialdried over sodium sulphate
10. filtrationfiltered
11. customevaporated
12. customPurification by chromatography (silica, 0 to 100% ethyl acetate in heptane)

ORD record

ord-4b4a287fbb7b4f499cdd1cb1e983bff7

Source dataset

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08466181B2