反应详情

温度

-78 °C

A solution of iPr2NH (11.2 mL, 80 mmol) in THF (100 mL) was cooled in an ice/salt bath and nBuLi (80 mmol) in hexanes (1.6M, 50 mL) was added dropwise. The solution was stirred for 1 h, then cooled to −78° C. A solution of 3-iodoacetophenone (19.7 g, 80 mmol) in THF (30 mL) was added dropwise and stirred for 1 h at −78° C., then a solution of methyl 4-fluorophenylacetate (13.4 g, 80 mmol) in THF (30 mL) was added. The mixture was stirred for 24 h while warming to RT. Acetic acid (9 mL) and EtOH (100 mL) were added, followed by MeNHNH2 (4.2 mL, 80 mmol). The mixture was heated to 60° C. for 1 h and, after cooling, the solvent was removed under reduced pressure. The residue was partitioned between CH2Cl2 and H2O, the CH2Cl2 layer was separated and retained and the aqueous layer re-extracted with CH2Cl2. The combined organic extracts were washed with brine, dried (MgSO4), and evaporated. The residue was purified by silica chromatography eluting with 50-80% CH2Cl2/iso-hexane to yield 3-(4-fluorobenzyl)-5-(3-iodophenyl)-1-methyl-1H-pyrazole, as the second of two pyrazole isomers, as a brown oil (4.5 g, 15%). 1H NMR (CDCl3, 500 MHz) δ 7.72 (1H, s), 7.69 (1H, d, J=8.0 Hz), 7.31 (1H, d, J=8.0 Hz), 7.26-7.20 (2H, m), 7.13 (1H, t, J=8.0 Hz), 6.96 (2H, t, J=8.8 Hz), 6.01 (1H, s), 3.93 (2H, s), 3.81 (3H, s). MS (ES+) C17H14FIN2 requires: 392, found: 393 (M+H+).

1. stirringstirred for 1 h at −78° C.
2. stirringThe mixture was stirred for 24 h
3. temperaturewhile warming to RT
4. temperatureThe mixture was heated to 60° C. for 1 h
5. temperatureafter cooling
6. customthe solvent was removed under reduced pressure
7. customThe residue was partitioned between CH2Cl2 and H2O
8. customthe CH2Cl2 layer was separated
9. extractionthe aqueous layer re-extracted with CH2Cl2
10. washThe combined organic extracts were washed with brine
11. dry with materialdried (MgSO4)
12. customevaporated
13. customThe residue was purified by silica chromatography
14. washeluting with 50-80% CH2Cl2/iso-hexane