Dimethylformamide → 4-Acetyl-2-chloro-5-hydroxybenzonitrile

HRID 626833Notes

Reaction equation

HRID 626833 reaction equation
Br[C:2]1[C:7]([Cl:8])=[CH:6][C:5]([C:9](=[O:11])[CH3:10])=[C:4]([OH:12])[CH:3]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.[CH3:55][N:56](C)C=O>[C-]#N.[Zn+2].[C-]#N.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:9]([C:5]1[C:4]([OH:12])=[CH:3][C:2]([C:55]#[N:56])=[C:7]([Cl:8])[CH:6]=1)(=[O:11])[CH3:10]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 595641771-(4-Bromo-5-chloro-2-hydroxyphenyl)ethanone

Product 1

HCID 866975254-Acetyl-2-chloro-5-hydroxybenzonitrileYield 72%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
120 °C

Procedure

1-(4-bromo-5-chloro-2-hydroxyphenyl)ethanone (6.2 g, 25 mmol) was combined with zinc cyanide (4.4 g, 37 mmol) in N,N-dimethylformamide (40 mL) degassed with nitrogen and tris(dibenzylideneacetone)dipalladium(0) (0.38 g, 0.42 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.57 g, 0.99 mmol) were added. The reaction was degassed with nitrogen and heated to 120° C. and monitored by LC/MS. After heating for 2 hrs, the reaction was allowed to cool to room temperature, diluted with ethyl acetate, and filtered to remove the solids. The organic layer was washed with water, brine, dried over magnesium sulfate and concentrated in vacuo to give the crude product. The product was purified by FCC on silica gel eluting hexane:ethyl acetate gradient to give 4-acetyl-2-chloro-5-hydroxybenzonitrile as a yellow crystalline solid (3.5 g, 72%).

Workup

  1. additionwere added
  2. customThe reaction was degassed with nitrogen
  3. temperatureAfter heating for 2 hrs
  4. temperatureto cool to room temperature
  5. additiondiluted with ethyl acetate
  6. filtrationfiltered
  7. customto remove the solids
  8. washThe organic layer was washed with water, brine
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated in vacuo
  11. customto give the crude product
  12. customThe product was purified by FCC on silica gel
  13. washeluting hexane

Sources & evidence

ORD record
ord-888e931804f44f959a9cc959d6523252
Source dataset
uspto-grants-2016_04
Patent number
US09309251B2

Reaction notes

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