Thionyl Chloride → 1,4-Dibenzyl-2-(chloromethyl)piperazine

HRID 2242814Notes

Reaction equation

S(Cl)([Cl:3])=O.[CH2:5]([N:12]1[CH2:17][CH2:16][N:15]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:14][CH:13]1[CH2:25]O)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1>C(Cl)(Cl)(Cl)Cl>[CH2:5]([N:12]1[CH2:17][CH2:16][N:15]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:14][CH:13]1[CH2:25][Cl:3])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1

Participants

Conditions

Temperature: 77 °C

Procedure

To the solution of thionyl chloride (1.63 ml, 22.4 mmol) in CCl4 (30 ml) was added the solution of (1,4-dibenzylpiperazin-2-yl)-methanol (2.74 g, 9.25 mmol) in CCl4 dropwise in 10 minutes. The produced suspension was stirred for 2 hours at 77° C. After cooled to room temperature, 20 ml of ice water was added and the aqueous layer was separated from the organic solvent. The PH of aqueous layer was adjusted to 12 with 4N NaOH aq., and extracted with CHCl3 three times. The combined organic layer was dried over MgSO4, and concentrated to give brownish oil which was purified by column chromatography on silica gel (CH2Cl2/MeOH=30/1) to give 1,4-dibenzyl-2-chloromethyl-piperazine in crude form (3.08 g, 95%, ca. 90% purity from HPLC analysis). The compound was used for next reaction without further purification: HPLC-MS (ESI): Calcd for C19H23ClN2[M+H]+ 315, found: 315.

Workup

temperatureAfter cooled to room temperature
customthe aqueous layer was separated from the organic solvent
extractionextracted with CHCl3 three times
dry with materialThe combined organic layer was dried over MgSO4
concentrationconcentrated
customto give brownish oil which
customwas purified by column chromatography on silica gel (CH2Cl2/MeOH=30/1)

Sources & evidence

ORD record: ord-8994f051478a417199a1b3c8a573aefd
Source dataset: uspto-grants-2010_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07674797B2

Reaction notes

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