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

HRID 1873980Notes

Reaction equation

HRID 1873980 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12].CO.C(Cl)[Cl:17]>>[Cl:17][CH2:9][C:8]([C:5]1[CH:6]=[CH:7][C:2]([F:1])=[C:3]([N+:11]([O-:13])=[O:12])[CH:4]=1)=[O:10]

Participants

4

Reactant 3

HCID 887Methanol2×HCID 6344DichloromethaneHCID 27346124'-Fluoro-3'-nitroacetophenone

Product 1

HCID 230367702-Chloro-1-(4-fluoro-3-nitrophenyl)ethan-1-one

Conditions

Temperature
0 °C

Procedure

1-(4-Fluoro-3-nitrophenyl)ethanone (18.4249 g; manufactured by Sigma-Aldrich Co.) was dissolved in CH2Cl2 (400 mL), added with methanol (3.04 mL), followed by replacement with nitrogen gas and cooling to 0° C. To the resulting solution, SO2Cl2-CH2Cl2 solution [109.32 mL; solution obtained 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 warming to room temperature. The reaction solution was cooled to 0° C., added with methanol (1.52 mL), and then SO2Cl2-CH2Cl2 solution [64.66 mL; solution obtained by dissolving SO2Cl2 (4.66 mL; manufactured by Wako Pure Chemical Industries, Ltd.) in CH2Cl2 (60 mL)] was added dropwise thereto. While warming 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. The solidified crystal, which had been obtained during purification of the resulting residue by column chromatography (“COLUMN-A”; n-hexane:ethyl acetate=88:12→67:33), was extracted with ethyl acetate, and then filtered. The filtrate was evaporated under reduced pressure, and as a result, the title compound was obtained (6.403 g).

Workup

  1. temperaturewhile warming to room temperature
  2. temperatureThe reaction solution was cooled to 0° C.
  3. temperatureWhile warming to room temperature
  4. stirringthe mixture was stirred for 3 hours
  5. washThe reaction solution was washed once with a saturated aqueous solution of sodium carbonate and once with brine
  6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  7. customthe solvent was evaporated under reduced pressure
  8. customThe solidified crystal, which had been obtained during purification of the resulting residue by column chromatography (“COLUMN-A”; n-hexane:ethyl acetate=88:12→67:33)
  9. extractionwas extracted with ethyl acetate
  10. filtrationfiltered
  11. customThe filtrate was evaporated under reduced pressure

Sources & evidence

ORD record
ord-e52785a2de564d93abd4e54f3b7bd31a
Source dataset
uspto-grants-2012_11
Patent number
US08304443B2

Reaction notes

Loading…