Реакция #2075726

Уравнение реакции

DMF

1-Bromo-4-chloro-2-fluoro-3-methoxybenzene

n-Butyllithium

→

title compound

Выход 61.0%

4-Chloro-2-fluoro-3-methoxybenzaldehyde

Выход 61.0%

Растворители

diethyl ether

Условия реакции

Обработка

1. 1
   Другое7,300,907 for preparation)
2. 2
   Другоеthe temperature below −70° C.
3. 3
   workup.ADDITIONduring the addition
4. 4
   Другоеthe temperature below −60° C
5. 5
   Температураto warm to ambient temperature
6. 6
   Другоеquenched with water
7. 7
   ДругоеThe organic phase was dried
8. 8
   Концентрированиеconcentrated
9. 9
   ДругоеThe product was purified by flash chromatography on silica gel (hexane/ethyl acetate gradient)

Методика

1-Bromo-4-chloro-2-fluoro-3-methoxybenzene (23.7 g, 99 mmol, see U.S. Pat. No. 7,300,907 for preparation) was dissolved in dry diethyl ether and cooled to −78° C. 2.5M n-Butyllithium in hexanes (44 mL, 110 mmol) was added in portions, keeping the temperature below −70° C. during the addition. DMF (15.5 mL, 200 mmol) was then added in portions, keeping the temperature below −60° C. The reaction mixture was then allowed to warm to ambient temperature and quenched with water. The organic phase was dried and concentrated. The product was purified by flash chromatography on silica gel (hexane/ethyl acetate gradient) to yield the title compound in sufficient purity for subsequent reactions (11.4 g, 61% yield): 1H NMR (CDCl3) δ 10.32 (s, 1H), 7.55 (m, 1H), 7.3 (m, 1H), 4.05 (d, 3H).

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