4-Bromoanisole → 1-(5-Bromo-2-hydroxyphenyl)-2-o-tolylethanone

HRID 1476150Notes

Reaction equation

HRID 1476150 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([OH:11])=O.C(Cl)(=O)C(Cl)=O.[Br: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>[Br:18][C:19]1[CH:20]=[CH:21][C:22]([OH:25])=[C:23]([C:9](=[O:11])[CH2:8][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[CH3:1])[CH:24]=1

Participants

7

Reactant 4

HCID 77304-BromoanisoleHCID 65578Oxalyl chlorideHCID 69519o-Tolylacetic acidHCID 6451240Aluminum(III) Chloride

Product 1

HCID 532343631-(5-Bromo-2-hydroxyphenyl)-2-o-tolylethanoneYield 33%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

2-Methylphenylacetic acid (9.60 g, 64.15 mmoles) was dissolved in 10 ml dichloromethane. To this mixture, oxalylchloride (7 ml, 80.19 mmoles) and DMF (3 drops) were added at 0° C. and stirred for 30 min. The solvent was evaporated and dissolved in 100 ml dichloromethane. To this mixture, 4-bromoanisole (10 g, 53.47 mmoles) was added and cooled to 0° C. At 0° C. AlCl3 (10.6 g, 80.19 mmoles) was added and the reaction mixture was warmed to RT and stirred for 24 h. The reaction mixture was quenched by the addition of 2N HCl and 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 white solid (5.5 g, 33% yield. 1H-NMR (δ ppm, DMSO-d6, 400 MHz): δ 11.52(s,1H), 8.02(d, J=2.4Hz, 1H), 7.65(dd, J=8.8, 2.5Hz, 1H), 7.16(m, 4H), 6.97(d, J=8.9Hz, 1H), 4.47(s, 2H), 2.14(s, 3H).

Workup

  1. customThe solvent was evaporated
  2. dissolutiondissolved in 100 ml dichloromethane
  3. customAt 0° C
  4. temperaturethe reaction mixture was warmed to RT
  5. stirringstirred for 24 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-31ede74168a041caaa3d88c753021cc7
Source dataset
uspto-grants-2015_04
Patent number
US09018375B2

Reaction notes

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