Dimethylformamide → HCID 22996206, compound

HRID 1167293Notes

Reaction equation

HRID 1167293 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[O:9][CH2:10][CH3:11].[CH3:12][N:13](C)C=O>C(OCC)C.C(=O)(O)[O-].[Na+].[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>[CH2:10]([O:9][C:3]1[CH:4]=[CH:5][C:6]([CH3:8])=[CH:7][C:2]=1[C:12]#[N:13])[CH3:11]

Participants

7

Reactant 2

HCID 6228DimethylformamideHCID 229962372-Bromo-1-ethoxy-4-methylbenzene

Product 1

HCID 22996206HCID 22996206, compoundYield 33%

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 3283Diethyl EtherSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
95 °C

Procedure

To a solution of 2-bromo-1-ethoxy-4-methyl-benzene (940 mg, 4.37 mmol) in dimethylformamide (5 mL) at room temperature was added zinc cyanide (513.1 mg, 4.37 mmol). The reaction mixture was degassed by passing argon through for 2 h before tetrakis(triphenylphosphine)palladium (505 mg, 0.437 mmol) was added. The reaction mixture was heated at 90-100° C. under argon for 12 h. The slurry reaction mixture was taken up in diethyl ether (10 mL) and sodium bicarbonate solution (2 mL). The product was extracted with diethyl ether (2×30 mL). The organic layers were washed with water (1×5 mL), brine (1×5 mL) 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 10% ethyl acetate in hexanes yielded 2-ethoxy-5-methyl-benzonitrile (232 mg, 33%).

Workup

  1. customThe reaction mixture was degassed
  2. customthrough for 2 h
  3. additionwas added
  4. customThe slurry reaction mixture
  5. extractionThe product was extracted with diethyl ether (2×30 mL)
  6. washThe organic layers were washed with water (1×5 mL), brine (1×5 mL)
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationThe solid was then filtered off
  9. concentrationthe filtrate was concentrated in vacuo
  10. customPurification of the crude residue by flash chromatography (Biotage system, KP-Sil™ 32-63 μm, 60 Å silica gel)
  11. washeluting with 10% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-088e5a22a5284980aacb40bf6464f5a9
Source dataset
uspto-grants-2003_09
Patent number
US06617346B1

Reaction notes

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