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

温度

-35 °C

To a suspension of 1-(4-fluoro-phenyl)-4-methyl-1H-[1,2,3]triazole (4.0 g, 23 mmol) in DME (114 mL) was added n-BuLi (1.6 M in hexane, 17.0 mL, 27 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 (2.03 g, 23 mmol) and LiCl (1.92 g, 45 mmol) in THF (32 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 (8.02 mL, 113 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 (160 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, dichloromethane) afforded the title compound (3.63 g, 69%) as an off white solid. 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, dichloromethane)

ORDレコード

ord-3f3bbfceb55447938bd801e23c25e9ea

出典データセット

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08466181B2