Methanol → 2-Chloro-1-(4-fluoro-3-nitrophenyl)ethan-1-one

Temperature

0 °C

1-(4-Fluoro-3-nitrophenyl)ethanone (18.4249 g; manufactured by Sigma-Aldrich Co.) was dissolved in CH2Cl2 (400 mL), and methanol (3.04 mL) was added thereto. The mixture was purged with nitrogen, and was cooled to 0° C. To this solution, a SO2Cl2—CH2Cl2 Solution [109.32 mL; solution prepared by dissolving SO2Cl2 (9.32 mL; manufactured by Wako Pure Chemical Industries, Ltd.) in CH2Cl2 (100 mL)] was added dropwise over 30 minutes, and the mixture was stirred overnight while the temperature was raised to room temperature. The reaction solution was cooled to 0° C., and methanol (1.52 mL) was added thereto. Subsequently, a SO2Cl2—CH2Cl2 solution [64.66 mL; solution prepared by dissolving SO2Cl2 (4.66 mL; manufactured by Wako Pure Chemical Industries, Ltd.) in CH2Cl2 (60 mL)] was added dropwise to the mixture, and while the temperature was raised to room temperature, the mixture was stirred for 3 hours. The reaction solution was washed once with a saturated aqueous solution of sodium carbonate, and once with brine. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. Subsequently, the resulting residue was purified by column chromatography (“COLUMN-A”; n-hexane:ethyl acetate=88:12→67:33), and in the middle of the chromatographic process, crystals solidified in the silica gel were extracted with ethyl acetate and filtered. The solvent of the filtrate was evaporated under reduced pressure, and thus the title compound (6.403 g) was obtained.

1. customThe mixture was purged with nitrogen
2. additionTo this solution, a SO2Cl2—CH2Cl2 Solution [109.32 mL; solution prepared by dissolving SO2Cl2 (9.32 mL; manufactured by Wako Pure Chemical Industries, Ltd.) in CH2Cl2 (100 mL)] was added dropwise over 30 minutes
3. temperaturewas raised to room temperature
4. temperatureThe reaction solution was cooled to 0° C.
5. additionmethanol (1.52 mL) was added
6. additionSubsequently, a SO2Cl2—CH2Cl2 solution [64.66 mL; solution prepared by dissolving SO2Cl2 (4.66 mL; manufactured by Wako Pure Chemical Industries, Ltd.) in CH2Cl2 (60 mL)] was added dropwise to the mixture
7. temperaturewhile the temperature was raised to room temperature
8. stirringthe mixture was stirred for 3 hours
9. washThe reaction solution was washed once with a saturated aqueous solution of sodium carbonate
10. dry with materialThe organic layer was dried over anhydrous sodium sulfate
11. customthe solvent was evaporated under reduced pressure
12. customSubsequently, the resulting residue was purified by column chromatography (“COLUMN-A”; n-hexane:ethyl acetate=88:12→67:33)
13. extractionwere extracted with ethyl acetate
14. filtrationfiltered
15. customThe solvent of the filtrate was evaporated under reduced pressure

ORD record

ord-e3dc326c9b5f4f4b9c808d4721bf8fab

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08008506B2