Hexamethyldisilazane → 1-(4-Bromophenyl)-2-ethyl-4,4,4-trifluoro-1,3-butanedione

To a solution of hexamethyldisilazane (4.92 g, 30.5 mmol) in THF (10 ml) was added dropwise n-BuLi (1.57 M hexane solution, 19.4 ml, 30.5 mmol) at −78° C. and the mixture was stirred at room temperature for 15 minutes. The mixture was cooled down to −78° C. again and 1-(4-bromophenyl)-1-butanone (5.77 g, 25.4 mmol) in THF (25 ml) was added dropwise over 15 min. The resulting mixture was stirred at −78° C. for 30 minutes, then allowed to warm up to 0° C. and stirred for 40 minutes. The solution was recooled down to −78° C. and N-trifluoroacetylimidazole (5.00 g, 30.5 mmol) was added. The mixture was stirred at −78° C. for 20 minutes, and at room temperature for 2 hours. The reaction was quenched with 2N HCl (30 ml). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (50 ml×2). The combined organic layer was washed with brine (50 ml), dried over Na2SO4, and concentrated in vacuo. The residue was chromatographed over silica gel with hexane/ethyl acetate (8:1 to 3:1) to give 5.64 g (69%) of the title compound as a oil.

1. temperatureThe mixture was cooled down to −78° C. again
2. stirringThe resulting mixture was stirred at −78° C. for 30 minutes
3. temperatureto warm up to 0° C.
4. stirringstirred for 40 minutes
5. additionwas added
6. stirringThe mixture was stirred at −78° C. for 20 minutes
7. waitat room temperature for 2 hours
8. customThe reaction was quenched with 2N HCl (30 ml)
9. customThe organic layer was separated
10. extractionthe aqueous layer was extracted with ethyl acetate (50 ml×2)
11. washThe combined organic layer was washed with brine (50 ml)
12. dry with materialdried over Na2SO4
13. concentrationconcentrated in vacuo
14. customThe residue was chromatographed over silica gel with hexane/ethyl acetate (8:1 to 3:1)

ORD record

ord-4a5f9841b0274c38ae22e83dcd91db93

Source dataset

uspto-grants-2003_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06603008B1