Dimethylformamide → HCID 86677823, compound

HRID 1499900Notes

Reaction equation

HRID 1499900 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) (Aldrich Catalog No. 328774) (1.0 g, 1.1 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (Aldrich Catalog No. 526460) (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 hrs 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 hrs the reaction
  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-090c3d25107149a18529f1f9c9f73194
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

Loading…