反应详情

温度

-70 °C

n-BuLi (2.5 M in hexanes, 105 mL) is slowly added to a solution of diisopropylamine (36.8 mL) in THF (600 mL) at 0° C. After 15 min, the mixture is cooled to −70° C. A solution of 3-bromo-2-chlorothiophene (49.4 g) in THF (20 mL) is added maintaining the internal temperature <−65° C. After 15 min, DMF (25.2 mL) is added. The mixture is stirred at −70° C. for 15 min and then allowed to warm to room temperature. The reaction mixture is quenched with saturated aq. NH4Cl solution (200 mL) and concentrated in vacuo to one-half volume. The residue is diluted with EtOAc (500 mL) and the aqueous layer is separated. The aqueous layer is extracted with EtOAc (2×100 mL). The combined organic layers are washed with brine (100 mL), dried (MgSO4), and concentrated to afford an oil. The oil is purified by column chromatography (heptane; heptane/EtOAc, 20/1; 10/1) and the resulting solid is suspended in heptane (75 mL) and filtered to afford 30.3 g (54%) of the title compound as a light yellow solid. Physical characteristics: M.p. 61-62° C.; 1H NMR (300 MHz, DMSO-d6) δ 9.82, 8.14; 13C NMR (100 MHz, CDCl3) δ 181.6, 140.9, 138.5, 138.1, 112.8.

1. temperaturemaintaining the internal temperature <−65° C
2. waitAfter 15 min
3. temperatureto warm to room temperature
4. customThe reaction mixture is quenched with saturated aq. NH4Cl solution (200 mL)
5. concentrationconcentrated in vacuo to one-half volume
6. additionThe residue is diluted with EtOAc (500 mL)
7. customthe aqueous layer is separated
8. extractionThe aqueous layer is extracted with EtOAc (2×100 mL)
9. washThe combined organic layers are washed with brine (100 mL)
10. dry with materialdried (MgSO4)
11. concentrationconcentrated
12. customto afford an oil
13. customThe oil is purified by column chromatography (heptane; heptane/EtOAc, 20/1; 10/1)
14. filtrationfiltered