反应详情

To a solution of 2-bromo-4-fluoro-benzoic acid tert-butyl ester (10.0 g, 36 mmol) in THF (100 mL) at −78° C. under an atmosphere of nitrogen was added lithium diisopropylamide (1.8M solution, 20 mL, 36 mmol) dropwise. The reaction mixture was stirred for 1.25 hours before adding DMF (10 mL) then stirred for a further 10 minutes before quenching with acetic acid (3 mL). The products were partitioned between ethyl acetate and water, the organic layer was separated, washed with brine, dried (Na2SO4), filtered and concentrated in vacuo to give a yellow oil which crystallized on standing. The crude product was triturated in cyclohexane to give the title compound as a yellow solid (6.8 g, 62%). 1H NMR (CDCl3, 400 MHz) 10.38 (1H, s), 7.80-7.73 (1H, m), 7.17 (1H, t, J=9.09 Hz), 1.62 (9H, s).

1. stirringthen stirred for a further 10 minutes
2. custombefore quenching with acetic acid (3 mL)
3. customThe products were partitioned between ethyl acetate and water
4. customthe organic layer was separated
5. washwashed with brine
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customto give a yellow oil which
10. customcrystallized
11. customThe crude product was triturated in cyclohexane