Bis(2-chloroethyl)amine hydrochloride → 1-[4,5-Dimethoxy-2-(3,3,5,5-tetramethylcyclohexyl)phenyl]piperazine

HRID 32221Notes

Reaction equation

HRID 32221 reaction equation
[CH3:1][O:2][C:3]1[C:8]([O:9][CH3:10])=[CH:7][C:6]([NH2:11])=[C:5]([CH:12]2[CH2:17][C:16]([CH3:19])([CH3:18])[CH2:15][C:14]([CH3:21])([CH3:20])[CH2:13]2)[CH:4]=1.Cl.Cl[CH2:24][CH2:25][NH:26][CH2:27][CH2:28]Cl>ClC1C=CC=CC=1Cl>[CH3:1][O:2][C:3]1[C:8]([O:9][CH3:10])=[CH:7][C:6]([N:11]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)=[C:5]([CH:12]2[CH2:17][C:16]([CH3:19])([CH3:18])[CH2:15][C:14]([CH3:21])([CH3:20])[CH2:13]2)[CH:4]=1

Participants

4

Reactant 2

HCID 522769Bis(2-chloroethyl)amine hydrochlorideHCID 231418854,5-Dimethoxy-2-(3,3,5,5-tetramethylcyclohexyl)phenylamine

Product 1

HCID 231415391-[4,5-Dimethoxy-2-(3,3,5,5-tetramethylcyclohexyl)phenyl]piperazine

Reagents, catalysts & solvents 1

HCID 72391,2-DichlorobenzeneSolvent

Conditions

Temperature
220 °C

Procedure

A mixture of the crude product of 4,5-dimethoxy-2-(3,3,5,5-tetramethylcyclohexyl)phenylamine produced in Example (87c), bis(2-chloroethyl)amine hydrochloride (700 mg, 3.91 mmol) and 1,2-dichlorobenzene (10 ml) was stirred for 2 hours at an external temperature of 220° C. During the reaction, nitrogen gas was blown in several times to remove the excess hydrogen chloride gas from the reactor. The reaction mixture was cooled to room temperature, saturated aqueous solution of sodium hydrogencarbonate was added and extraction was performed with chloroform. The aqueous layer was again extracted with chloroform, and the organic layers were combined, washed with brine and then dried over anhydrous magnesium sulfate. The desiccant was filtered off and the filtrate was concentrated under reduced pressure. The resultant residue was purified by NH silica gel column chromatography (ethyl acetate/heptane) to give 490 mg of the title compound as a brown oil.

Workup

  1. customDuring the reaction, nitrogen gas
  2. customto remove the excess hydrogen chloride gas from the reactor
  3. temperatureThe reaction mixture was cooled to room temperature
  4. additionsaturated aqueous solution of sodium hydrogencarbonate was added
  5. extractionextraction
  6. extractionThe aqueous layer was again extracted with chloroform
  7. washwashed with brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationThe desiccant was filtered off
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. customThe resultant residue was purified by NH silica gel column chromatography (ethyl acetate/heptane)

Sources & evidence

ORD record
ord-cc38b488a4a949d39335cca206921093
Source dataset
uspto-grants-2008_09
Patent number
US07425554B2

Reaction notes

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