Dimethylformamide → HCID 86677823, compound

HRID 1499907Notes

Reaction equation

HRID 1499907 reaction equation
Br[C:2]1[C:7]([CH3:8])=[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]([CH3:8])[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 425530931-(4-Bromo-2-hydroxy-5-methylphenyl)ethan-1-one

Product 1

HCID 86677823HCID 86677823, compoundYield 98%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

The 1-(4-bromo-2-hydroxy-5-methylphenyl)ethanone (8.5 g, 37 mmol, Alfa Aesar catalog#H29125) was combined with zinc cyanide (8.7 g, 74 mmol) in N,N-dimethylformamide (75 mL) degassed with nitrogen and the tris(dibenzylideneacetone)dipalladium(0) (1.0 g, 1.1 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (1.5 g, 2.6 mmol) were added. The reaction was degassed again with nitrogen and heated to 120° C. and monitored by LC/MS. After heating for 18 h, the reaction was complete, the reaction was allowed to cool to room temperature, taken up in ethyl acetate and washed with water (2×), brine, dried over magnesium sulfate and concentrated to give the crude product as a dark amber oil. The product was purified by FCC on silica gel eluting hexane:ethyl acetate gradient to give 4-acetyl-5-hydroxy-2-methylbenzonitrile as a solid (6.3 g, 98%). LCMS calculated for C10H10NO2 (M+H)+: m/z=176.1; found: 176.2.

Workup

  1. customdegassed with nitrogen
  2. customThe reaction was degassed again with nitrogen
  3. temperatureAfter heating for 18 h
  4. temperatureto cool to room temperature
  5. washwashed with water (2×), brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated
  8. customto give the crude product as a dark amber oil
  9. customThe product was purified by FCC on silica gel
  10. washeluting hexane

Sources & evidence

ORD record
ord-802919be326c4b5daa683e50264b951f
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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