4-Fluoroanisole → 1-(5-Fluoro-2-hydroxyphenyl)-2-(3-fluorophenyl)ethanone

HRID 1484302Notes

Reaction equation

HRID 1484302 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]([OH:11])=O)[CH:5]=[CH:6][CH:7]=1.C(Cl)(=O)C(Cl)=O.[F:18][C:19]1[CH:24]=[CH:23][C:22]([O:25]C)=[CH:21][CH:20]=1.[Al+3].[Cl-].[Cl-].[Cl-]>ClCCl.CN(C=O)C>[F:18][C:19]1[CH:20]=[CH:21][C:22]([OH:25])=[C:23]([C:9](=[O:11])[CH2:8][C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=2)[CH:24]=1

Participants

7

Reactant 4

HCID 99874-FluoroanisoleHCID 65578Oxalyl chlorideHCID 676173-Fluorophenylacetic acidHCID 6451240Aluminum(III) Chloride

Product 1

HCID 532346871-(5-Fluoro-2-hydroxyphenyl)-2-(3-fluorophenyl)ethanoneYield 45%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

3-Fluorophenylacetic acid (7.33 g, 47.56 mmoles) was dissolved in 25 ml dichloromethane. To this mixture, oxalylchloride (7.54 g, 59.46 mmoles) and DMF (3 drops) were added at 0° C. and stirred for 30 min. The solvent was evaporated and dissolved in 25 ml dichloromethane. To this mixture, 4-fluoroanisole (5.00 g, 39.64 mmoles) was added and cooled to 0° C. At 0° C. AlCl3 (7.95 g, 59.46 mmoles) was added and the reaction mixture was warmed to RT and stirred for 12 h. The reaction mixture was quenched by the addition of 2N HCl, extracted with ethyl acetate, dried over sodium sulphate and concentrated. The crude product was purified by column chromatography with ethyl acetate:petroleum ether to afford the title compound as colourless solid (4.5 g, 45% yield. 1H-NMR (δ ppm, DMSO-D6, 400 MHz): δ 11.34 (s, 1H), 7.75 (dd, J=9.4, 3.1 Hz, 1H), 7.42 (m, 2H), 7.12 (m, 3H), 7.05 (dd, J=9.0, 4.5 Hz, 1H), 4.47 (s, 2H).

Workup

  1. customThe solvent was evaporated
  2. dissolutiondissolved in 25 ml dichloromethane
  3. customAt 0° C
  4. temperaturethe reaction mixture was warmed to RT
  5. stirringstirred for 12 h
  6. customThe reaction mixture was quenched by the addition of 2N HCl
  7. extractionextracted with ethyl acetate
  8. dry with materialdried over sodium sulphate
  9. concentrationconcentrated
  10. customThe crude product was purified by column chromatography with ethyl acetate

Sources & evidence

ORD record
ord-27b6cedf01a44ab186af07df9558b7ed
Source dataset
uspto-grants-2016_08
Patent number
US09421209B2

Reaction notes

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