Dimethylacetamide → Acetamide, N-(4-cyano-2-fluorophenyl)-

HRID 400597

Reaction equation

HRID 400597 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:11])[CH3:10])=[C:4]([F:12])[CH:3]=1.C[C:14]([N:16](C)C)=O>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>[C:14]([C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:11])[CH3:10])=[C:4]([F:12])[CH:3]=1)#[N:16]

Participants

6

Reactant 2

HCID 31374DimethylacetamideHCID 67593N-(4-bromo-2-fluorophenyl)acetamide

Product 1

HCID 11344323Acetamide, N-(4-cyano-2-fluorophenyl)-Yield 86%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

A solution of N-(4-bromo-2-fluorophenyl)acetamide (12.9 g, 55.4 mmol) in 125 mL of anhydrous dimethyl acetamide was heated in the presence of zinc cyanide (5.53 g, 47.1 mmol) and tetrakis(triphenylphosphine)palladium (0) (5.2 g, 4.5 mmol) at 100° C. for 3 hours. The mixture was diluted with 300 mL of cold water, the resulting solid was filtered, washed with water, and dried. The filtrate was extracted with three 100 mL portions of ethyl acetate and the combined extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting residue was combined with the solid from the filtration. This combined material was filtered through a silica gel column (100% dichloromethane followed by 100% ethyl acetate) to give 8.5 g of N-(4-cyano-2-fluorophenyl)acetamide as a light cream solid (86% yield).

Workup

  1. filtrationthe resulting solid was filtered
  2. washwashed with water
  3. customdried
  4. extractionThe filtrate was extracted with three 100 mL portions of ethyl acetate
  5. dry with materialthe combined extracts were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. filtrationThe resulting residue was combined with the solid from the filtration
  9. filtrationThis combined material was filtered through a silica gel column (100% dichloromethane followed by 100% ethyl acetate)

Sources & evidence

ORD record
ord-14d7c05b20334194b88414297225deb0
Source dataset
uspto-grants-2014_06
Patent number
US08741897B2

Linked notes

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