反应详情

温度

-35 °C

2,4-Dichloro-6-iodophenol (2.0 grams (g), 6.9 millimoles (mmol)) was dissolved in dry tetrahydrofuran (THF; 20 milliliters (mL)), cooled to −30 to −40° C., treated in portions with isopropyl magnesium chloride-lithium chloride complex (1.3 M in THF; 7.3 mmol) and stirred for 45 minutes (min) as the temperature was allowed to rise to 0° C. The mixture was cooled to −30° C., treated with 8 mL (10 mmol) of the Grignard reagent and stirred for 30 min at −30° C. Ethyl trifluoroacetate (2.4 mL, 2.8 g, 20 mmol) was added, and the mixture was stirred for 15 min at −30° C., warmed to 25° C. and stirred for 2 hours (h). The reaction was quenched by addition of saturated (satd) ammonium chloride (NH4C1; 10 mL), diluted with ethyl acetate (EtOAc; 50 mL) and washed with 1 M hydrochloric acid (HCl; 20 mL), satd sodium chloride (NaCl; 10 mL), dried over sodium sulfate (Na2SO4) and evaporated. The residue was purified by silica gel chromatography with 0-20% EtOAc/hexane to give the purified ketone (1.2 g): mp 50-52° C.; 1H NMR (400 MHz, CDCl3) δ 7.61 (d, J=2.4 Hz, 1H), 7.34 (d, J=2.4 Hz, 1H), 5.92 (s, 1H); EIMS m/z 258.

1. customto rise to 0° C
2. temperatureThe mixture was cooled to −30° C.
3. stirringstirred for 30 min at −30° C
4. stirringthe mixture was stirred for 15 min at −30° C.
5. temperaturewarmed to 25° C.
6. stirringstirred for 2 hours (h)
7. customThe reaction was quenched by addition of saturated (satd) ammonium chloride (NH4C1; 10 mL)
8. additiondiluted with ethyl acetate (EtOAc; 50 mL)
9. washwashed with 1 M hydrochloric acid (HCl; 20 mL), satd sodium chloride (NaCl; 10 mL)
10. dry with materialdried over sodium sulfate (Na2SO4)
11. customevaporated
12. customThe residue was purified by silica gel chromatography with 0-20% EtOAc/hexane