反应详情

Into a dry, nitrogen-flushed 250 mL round-bottom flask was placed 4.0 g of 4-bromoaniline (23 mmol). After addition of THF (30 mL), the resulting solution was cooled in an ice bath. 14 mL of a 1.6 M solution in hexane of butyllithium (22 mmol) was added dropwise to the 4-bromoaniline solution to afford a beige suspension. After 10 minutes stirring, the cold suspension was treated with 6.0 g of 5-(bromomethyl)-1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole (18 mmol) as a solution in THF (30 mL) via cannula. The flask and cannula were then rinsed with additional THF (10 mL) to insure complete transfer of the bromide. After 1 hour stirring at 0° C., LC/MS analysis showed no remaining 5-(bromomethyl)-1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazole, and showed a large peak for the desired product. After 100 min., the reaction was quenched by the addition of 1 mL of acetic acid (18 mmol). The resulting pale suspension was concentrated in vacuo to afford a pale brown foam. The crude product was purified by silica gel flash chromatography using gradient elution from 0% to 70% EtOAc/hexane. Many of the column fractions were impure. Pure fractions were concentrated in vacuo to afford 4-bromo-N-((1-(2-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)aniline as a pale yellow oil, yield: 2.35 g (31%); 1H NMR (400 MHz, CDCl3): δ 7.59-7.55 (m, 1H), 7.52-7.45 (m, 1H), 7.44-7.40 (m, 2H), 7.25-7.21 (m, 2H), 6.63 (s, 1H), 6.41-6.37 (m, 2H), 4.20 (br s, 2H), 3.90 (br s, 1H); MS (ESI) m/z 432.0 [M+H]+.

1. customInto a dry, nitrogen-flushed 250 mL round-bottom flask
2. temperaturethe resulting solution was cooled in an ice bath
3. customto afford a beige suspension
4. washThe flask and cannula were then rinsed with additional THF (10 mL)
5. stirringAfter 1 hour stirring at 0° C.
6. waitAfter 100 min.
7. concentrationThe resulting pale suspension was concentrated in vacuo
8. customto afford a pale brown foam
9. customThe crude product was purified by silica gel flash chromatography
10. washelution from 0% to 70% EtOAc/hexane
11. concentrationPure fractions were concentrated in vacuo