N,N,N',N'-Tetramethylethylenediamine → 4-Acetyl-2-fluorobenzonitrile

HRID 500133

Reaction equation

HRID 500133 reaction equation
C[N:2](C)[CH2:3][CH2:4]N(C)C.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.BrC1[CH:57]=[CH:56][C:55]([C:58](=[O:60])[CH3:59])=[CH:54][C:53]=1[F:61]>CN(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:58]([C:55]1[CH:56]=[CH:57][C:4]([C:3]#[N:2])=[C:53]([F:61])[CH:54]=1)(=[O:60])[CH3:59]

Participants

7

Conditions

Temperature
160 °C

Procedure

N,N,N′,N′-Tetramethylethylenediamine (0.667 mL, 4.42 mmol), zinc cyanide (1.46 g, 12.4 mmol), tris(dibenzylideneacetone)dipalladium(0) (54.05 mg, 0.059 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (124.3 mg, 0.215 mmol) was added successively to a solution of 1-(4-bromo-3-fluorophenyl)ethanone (4.34 g, 20.0 mmol) in N,N-dimethylformamide (15 mL) in a microwave tube. The tube was sealed and degassed three times, and heated to 160° C. under microwave irradiation with a 240 s hold time, and 300 Watt maximum power input. After cooling, the reaction mixture was filtered through a pad of Celite with a thin layer of silica gel in the middle using dichloromethane as the eluant. The combined filtrates were concentrated under reduced pressure. The residue was purified by chromatography on silica gel with ethyl acetate in hexanes (0-40%) to give the desired product. (3.20 g, 98.1%).

Workup

  1. customThe tube was sealed
  2. customdegassed three times
  3. temperatureAfter cooling
  4. filtrationthe reaction mixture was filtered through a pad of Celite with a thin layer of silica gel in the middle
  5. concentrationThe combined filtrates were concentrated under reduced pressure
  6. customThe residue was purified by chromatography on silica gel with ethyl acetate in hexanes (0-40%)

Sources & evidence

ORD record
ord-77ff4e5b5c7244ae8e31d1c30552ca0c
Source dataset
uspto-grants-2010_08
Patent number
US07767675B2

Linked notes

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