Bis(2-chloroethyl)amine hydrochloride → 1-(2-Cycloheptylphenyl)piperazine

HRID 2218800Notes

Reaction equation

HRID 2218800 reaction equation
[CH:1]1([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[NH2:14])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.Cl[CH2:17][CH2:18][NH:19][CH2:20][CH2:21]Cl>ClC1C=CC=CC=1Cl>[CH:1]1([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[N:14]2[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]1

Participants

4

Reactant 2

HCID 522769Bis(2-chloroethyl)amine hydrochlorideHCID 109432572-Cycloheptylphenylamine

Product 1

HCID 231425011-(2-Cycloheptylphenyl)piperazineYield 73.3%

Reagents, catalysts & solvents 1

HCID 72391,2-DichlorobenzeneSolvent

Conditions

Temperature
200 °C

Procedure

To a solution of the 2-cycloheptylphenylamine (539 mg, 2.85 mmol) produced in Example (44b) in 1,2-dichlorobenzene (7 mL) was added bis(2-chloroethyl)amine hydrochloride (610 mg, 3.42 mmol), and the mixture was stirred at an external temperature of 200° C. under a nitrogen atmosphere. During the reaction, a nitrogen stream was blown into the reactor to remove the hydrogen chloride gas in the reactor. This procedure was repeated several times. After 8 hours, the mixture was air-cooled to room temperature. To the reaction mixture were added aqueous solution of potassium carbonate, ethyl acetate and methanol, and extraction was performed three times with ethyl acetate. The obtained organic layers were dried over anhydrous sodium sulfate, and then the desiccant was filtered off and the filtrate was concentrated under reduced pressure. The obtained residue was purified by NH silica gel column chromatography (ethyl acetate/heptane) to give 540 mg of the title compound as a brown oil.

Workup

  1. customDuring the reaction
  2. customto remove the hydrogen chloride gas in the reactor
  3. temperaturethe mixture was air-cooled to room temperature
  4. additionTo the reaction mixture were added aqueous
  5. extractionsolution of potassium carbonate, ethyl acetate and methanol, and extraction
  6. dry with materialThe obtained organic layers were dried over anhydrous sodium sulfate
  7. filtrationthe desiccant was filtered off
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe obtained residue was purified by NH silica gel column chromatography (ethyl acetate/heptane)

Sources & evidence

ORD record
ord-01787a5d2aff464b978a6f7924f7fbe7
Source dataset
uspto-grants-2008_08
Patent number
US07410971B2

Reaction notes

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