Hydrochloric Acid → Piperazine, 1-[4-bromo-2-(1,1-dimethylethyl)phenyl]-, hydrochloride (1:2)

HRID 534822Notes

Reaction equation

[Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([C:9]([CH3:12])([CH3:11])[CH3:10])[CH:3]=1.[ClH:13].[Cl:14][CH2:15][CH2:16][NH:17][CH2:18][CH2:19]Cl.[OH-].[Na+].Cl>COCCOCCOC.C(OCC)(=O)C.CCOCC>[ClH:14].[ClH:13].[Br:1][C:2]1[CH:8]=[CH:7][C:5]([N:6]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)=[C:4]([C:9]([CH3:12])([CH3:11])[CH3:10])[CH:3]=1

Participants

Conditions

Temperature: 170 °C

Procedure

A suspension of 4-bromo-2-tert-butylaniline (Reference Example 8, 25.0 g, 110 mmol) and bis(2-chloroethyl)amine hydrochloride (21.5 g, 120 mmol) in diethylene glycol dimethyl ether (157 mL) was stirred for 3 days at 170° C. It was cooled to room temperature, added 1 M sodium hydroxide solution (50 mL), and extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give crude product. It was diluted with ethyl acetate and ether (50:50) and added 1 M hydrochloric acid solution to provide 1-(4-bromo-2-tert-butylphenyl)piperazine dihydrochloride (16.2 g, 40%) as a gray solid.

Workup

temperatureIt was cooled to room temperature
extractionextracted with ethyl acetate
washThe extract was washed with brine
dry with materialdried over anhydrous magnesium sulfate
concentrationconcentrated under reduced pressure
customto give crude product

Sources & evidence

ORD record: ord-aded8697d3b843e78c6180e5a9014580
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08853215B2

Reaction notes

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