Hydrochloric Acid → Tert-butyl 4-(4-(2-chloro-2-cyanovinyl)phenyl)piperazine-1-carboxylate

HRID 336841Notes

Reaction equation

HRID 336841 reaction equation
O.NN.[CH:4]([C:6]1[CH:11]=[CH:10][C:9]([N:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]2)=[CH:8][CH:7]=1)=O.C(N(CC)CC)C.[Cl:32][C:33](Cl)(Cl)[C:34]#[N:35].Cl>CS(C)=O.[Cu]Cl>[Cl:32][C:33]([C:34]#[N:35])=[CH:4][C:6]1[CH:11]=[CH:10][C:9]([N:12]2[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]2)=[CH:8][CH:7]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 11011TrichloroacetonitrileHCID 24654Hydrazine hydrate (1:1)HCID 2795509Tert-butyl 4-(4-formylphenyl)piperazine-1-carboxylate

Product 1

HCID 86671383Tert-butyl 4-(4-(2-chloro-2-cyanovinyl)phenyl)piperazine-1-carboxylateYield 26.6%

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 679Dimethyl SulfoxideSolvent3×

Procedure

To a solution of hydrazine hydrate diluted in 16 ml of dimethylsulfoxide under argon are added dropwise a solution of 4.76 g (16.41 mmol) of tert-butyl 4-(4-formylphenyl)piperazine-1-carboxylate dissolved in 32 ml of dimethylsulfoxide. The reaction mixture is stirred at room temperature for 3 h before being cooled over an ice bath. Then, the successive addition is made of 11.45 ml (82 mmol) of triethylamine, 162 mg of copper (I) chloride and, in 5 min, a solution of 8.23 ml (82 mmol) of trichloroacetonitrile diluted in 16 ml of dimethylsulfoxide. The reaction mixture is stirred at room temperature for 18 h then poured onto an aqueous 0.1N hydrochloric acid solution. The product is extracted several times with dichloromethane. The organic phases are combined, dried over magnesium sulfate, and concentrated. The residue is purified by chromatography on silica (cyclohexane/ethyl acetate eluent: 8:2) to yield 1.52 g (26%) of tert-butyl 4-(4-(2-chloro-2-cyanovinyl)phenyl)piperazine-1-carboxylate in the form of a yellow solid (mixture of the two isomers Z/E).

Workup

  1. temperaturebefore being cooled over an ice bath
  2. additionThen, the successive addition
  3. stirringThe reaction mixture is stirred at room temperature for 18 h
  4. extractionThe product is extracted several times with dichloromethane
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. customThe residue is purified by chromatography on silica (cyclohexane/ethyl acetate eluent: 8:2)

Sources & evidence

ORD record
ord-346a03a009ad4e659dcb0eb89eabc413
Source dataset
uspto-grants-2014_11
Patent number
US08889711B2

Reaction notes

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