Bis(2-chloroethyl)amine hydrochloride → 1-[3-Fluoro-2-(3,3,5,5-tetramethylcyclohex-1-enyl)phenyl]piperazine

HRID 32238Notes

Reaction equation

HRID 32238 reaction equation
[F:1][C:2]1[C:3]([C:9]2[CH2:14][C:13]([CH3:16])([CH3:15])[CH2:12][C:11]([CH3:18])([CH3:17])[CH:10]=2)=[C:4]([NH2:8])[CH:5]=[CH:6][CH:7]=1.Cl.Cl[CH2:21][CH2:22][NH:23][CH2:24][CH2:25]Cl>ClC1C=CC=CC=1Cl>[F:1][C:2]1[C:3]([C:9]2[CH2:14][C:13]([CH3:16])([CH3:15])[CH2:12][C:11]([CH3:18])([CH3:17])[CH:10]=2)=[C:4]([N:8]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 522769Bis(2-chloroethyl)amine hydrochlorideHCID 231430383-Fluoro-2-(3,3,5,5-tetramethylcyclohex-1-enyl)phenylamine

Product 1

HCID 231430121-[3-Fluoro-2-(3,3,5,5-tetramethylcyclohex-1-enyl)phenyl]piperazineYield 26.8%

Reagents, catalysts & solvents 1

HCID 72391,2-DichlorobenzeneSolvent

Conditions

Temperature
200 °C

Procedure

To a solution of 3-fluoro-2-(3,3,5,5-tetramethylcyclohex-1-enyl)phenylamine (623 mg, 2.52 mmol) produced in Example (97c) in 1,2-dichlorobenzene (7 mL) was added bis(2-chloroethyl)amine hydrochloride (560 mg, 3.14 mmol), followed by reflux for 5 hours at an external temperature of 200° C. under a nitrogen atmosphere. During the reaction, a nitrogen stream was circulated into the reactor several times to remove the hydrogen chloride gas. After cooling the reaction mixture to room temperature, ethyl acetate, tetrahydrofuran, methanol, saturated aqueous solution of sodium carbonate and water were added for partition between oil and water. The aqueous layer was further extracted with ethyl acetate, and the combined organic layer was dried over anhydrous sodium 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 214 mg of the title compound as a light brown oil.

Workup

  1. customDuring the reaction
  2. customto remove the hydrogen chloride gas
  3. temperatureAfter cooling the reaction mixture to room temperature
  4. additionethyl acetate, tetrahydrofuran, methanol, saturated aqueous solution of sodium carbonate and water were added
  5. customfor partition between oil and water
  6. extractionThe aqueous layer was further extracted with ethyl acetate
  7. dry with materialthe combined organic layer was dried over anhydrous sodium sulfate
  8. filtrationThe desiccant was filtered off
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customThe resultant residue was purified by NH silica gel column chromatography (ethyl acetate/heptane)

Sources & evidence

ORD record
ord-1d34dbfa627b47b6ae5be8a9b52c8930
Source dataset
uspto-grants-2008_09
Patent number
US07425554B2

Reaction notes

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