Dimethylformamide → 2-Hydroxy-4-methoxybenzonitrile

HRID 1167311Notes

Reaction equation

HRID 1167311 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[OH:10].[CH3:11][N:12](C)C=O>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:10][C:3]1[CH:4]=[C:5]([O:8][CH3:9])[CH:6]=[CH:7][C:2]=1[C:11]#[N:12]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 134938392-Bromo-5-methoxyphenol

Product 1

HCID 114236802-Hydroxy-4-methoxybenzonitrileYield 16%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
95 °C

Procedure

Zinc cyanide (1.282 g, 0.770 mmol) and 2-bromo-5-methoxy-phenol (3 g, 14.18 mmol) were taken into dimethylformamide (15 mL) and the mixture was degassed with argon for 45 min. To this was added tetrakis(triphenylphosphine)palladium (993 mg, 0.852 mmol), and the reaction mixture was sealed after being degassed for 30 min. After heated at 95° C. for 2 d, the reaction mixture was cooled to room temperature and worked up with water and diethyl ether. The ethereal extracts were washed with brine and dried over anhydrous sodium sulfate. The solid was then filtered off, and the filtrate was concentrated in vacuo. Purification of the crude residue by flash chromatography (Biotage system, KP-Sil™ 32-63 μm, 60 Å silica gel) eluting with 0-25% ethyl acetate in hexanes yielded 2-hydroxy-4-methoxy-benzonitrile (334 mg, 16%).

Workup

  1. customthe mixture was degassed with argon for 45 min
  2. customthe reaction mixture was sealed
  3. customafter being degassed for 30 min
  4. temperaturethe reaction mixture was cooled to room temperature
  5. washThe ethereal extracts were washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationThe solid was then filtered off
  8. concentrationthe filtrate was concentrated in vacuo
  9. customPurification of the crude residue by flash chromatography (Biotage system, KP-Sil™ 32-63 μm, 60 Å silica gel)
  10. washeluting with 0-25% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-3a46c6055a8e4bfeafcf9042be867370
Source dataset
uspto-grants-2003_09
Patent number
US06617346B1

Reaction notes

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