反应详情

温度

-85 °C

To an oven-dried, N2-purged 1-L, round-bottomed flask containing a large magnetic stir bar were added via syringe anhydrous tetrahydrofuran (200 mL) and tetramethylethylenediamine (11.3 mL, 8.72 g, 75.0 mmol). The flask was cooled to −85° C. (dry ice/anhydrous ether slurry) and the sec-butyllithium/cyclohexane solution (53.6 mL of 1.4 M solution, 75.0 mmol) was added via syringe. A solution of commercially available 3-chloro-4-fluorobenzoic acid (5.24 g, 30 mmol) in anhydrous tetrahydrofuran (10 mL) was added dropwise to the reaction via syringe. The resulting orange/brown slurry was stirred at −85° C. for 2 hours. A solution of hexachloroethane (28.4 g, 120 mmol) in anhydrous tetrahydrofuran (30 mL) was added dropwise to the reaction mixture. The mixture was stirred at −85° C. for 1 hour and then allowed to warm to room temperature over 4 hours. The solvents/volatiles were removed by rotary evaporator to give a brown semi-solid. Water (150 mL) was added. The mixture was transferred to a separatory funnel and washed with ether (2×100 mL). Hydrochloric acid (1 N) was added via pipette to adjust the pH to ˜1. The mixture was extracted with ethyl acetate (4×100 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated by rotary evaporator to give a tan solid. The product was recrystallized from ethyl acetate/hexanes to give 4.36 g (70%) of the title compound as a fine white powder. MS (ESI−) m/z 206.9 (M−H); 1H NMR (DMSO-d6) δ 7.54 (dd, J=8.8, 8.8 Hz, 1H), 7.85 (dd, J=8.8, 5.8 Hz, 1H), 13.72 (br s, 1H).

1. customTo an oven-dried, N2-purged 1-L, round-bottomed flask
2. additioncontaining a large magnetic stir bar
3. stirringThe mixture was stirred at −85° C. for 1 hour
4. temperatureto warm to room temperature over 4 hours
5. customThe solvents/volatiles were removed by rotary evaporator
6. customto give a brown semi-solid
7. customThe mixture was transferred to a separatory funnel
8. washwashed with ether (2×100 mL)
9. additionHydrochloric acid (1 N) was added via pipette
10. extractionThe mixture was extracted with ethyl acetate (4×100 mL)
11. dry with materialThe combined organic extracts were dried over magnesium sulfate
12. filtrationfiltered
13. concentrationconcentrated by rotary evaporator
14. customto give a tan solid
15. customThe product was recrystallized from ethyl acetate/hexanes