Ethylenediamine → 2-Amino-4,5-difluoro-3-methylthiomethylbenzonitrile

HRID 1638652Notes

Reaction equation

HRID 1638652 reaction equation
Br[C:2]1[C:7]([NH2:8])=[C:6]([CH2:9][S:10][CH3:11])[C:5]([F:12])=[C:4]([F:13])[CH:3]=1.[CH3:14][N:15](P(N(C)C)(N(C)C)=O)C.[Cu](C#N)C#N.C(N)CN>O>[NH2:8][C:7]1[C:6]([CH2:9][S:10][CH3:11])=[C:5]([F:12])[C:4]([F:13])=[CH:3][C:2]=1[C:14]#[N:15]

Participants

6

Reactant 4

HCID 3301EthylenediamineHCID 12679HexamethylphosphoramideHCID 15631820HCID 15631820, compoundHCID 178418260HCID 178418260, compound

Product 1

HCID 156318212-Amino-4,5-difluoro-3-methylthiomethylbenzonitrileYield 35.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 6-bromo-3,4-difluoro-2-methylthiomethylaniline (99 g), HMPA (130 g) and copper cyanide (48 g) is heated at 150° C. for 4 hours. After cooling, the reaction mixture is poured into a solution of ethylenediamine (50 ml) in water (500 ml), and the mixture is heated at 60° C. for one hour. After cooling, the mixture is extracted with ethyl acetate, and the extract is dried over magnesium sulfate and concentrated. The resulting residue is purified by silica gel column chromatography (solvent, dichloromethane:n-hexane=1:1), and the product is recrystallized from ethanol to give 2-amino-4,5-difluoro-3-methylthiomethylbenzonitrile (28 g), as a white crystal, m.p. 109°-110° C.

Workup

  1. temperatureAfter cooling
  2. temperaturethe mixture is heated at 60° C. for one hour
  3. temperatureAfter cooling
  4. extractionthe mixture is extracted with ethyl acetate
  5. dry with materialthe extract is dried over magnesium sulfate
  6. concentrationconcentrated
  7. customThe resulting residue is purified by silica gel column chromatography (solvent, dichloromethane:n-hexane=1:1)
  8. customthe product is recrystallized from ethanol

Sources & evidence

ORD record
ord-d4444ba466ad4b4f93da464befc3d2dd
Source dataset
uspto-grants-1989_11
Patent number
US04880806

Reaction notes

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