反应详情

温度

-70 °C

To a solution of 2-fluoro-4-iodo-aniline (2.24 g, 9.43 mmol) in anhydrous THF (30 ml) under an atmosphere of nitrogen was added 1M LHMDS in hexanes (18 ml, 1M, 18.0 mmol) keeping the internal temperature below −65° C. After complete addition the reaction mixture was stirred for 30 minutes at −70° C. A solution of 2-dimethoxymethyl-1,3-difluoro-4-nitro-benzene (2.0 g, 8.58 mmol) in anhydrous THF (20 ml) was added to the reaction mixture keeping the internal temperature below −68° C. After complete addition the reaction mixture was stirred for 30 minutes at −70° C. then allowed to warm to room temperature and stirred for 22 hours. The reaction was quenched with saturated aqueous NH4Cl solution and extracted with ethyl acetate (200 ml). The organic layer was washed with brine, dried (Na2SO4), concentrated in vacuo to a minimum volume and triturated with cyclohexane to yield the title compound (2.18 g, 56%). LCMS (Method B): RT=4.26 min, [M−H]−=449.

1. customthe internal temperature below −65° C
2. additionAfter complete addition the reaction mixture
3. customthe internal temperature below −68° C
4. additionAfter complete addition the reaction mixture
5. stirringwas stirred for 30 minutes at −70° C.
6. temperatureto warm to room temperature
7. stirringstirred for 22 hours
8. customThe reaction was quenched with saturated aqueous NH4Cl solution
9. extractionextracted with ethyl acetate (200 ml)
10. washThe organic layer was washed with brine
11. dry with materialdried (Na2SO4)
12. concentrationconcentrated in vacuo to a minimum volume
13. customtriturated with cyclohexane