Hydrochloric Acid → 1-[(4-Chlorophenyl)(phenyl)methyl]piperazine--hydrogen chloride (1/2)

HRID 392861Notes

Reaction equation

[ClH:1].[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:10]2[CH2:15][CH2:14][N:13](C(OC(C)(C)C)=O)[CH2:12][CH2:11]2)=[CH:5][CH:4]=1>C(OCC)(=O)C>[ClH:2].[ClH:1].[Cl:2][C:3]1[CH:4]=[CH:5][C:6]([CH:9]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[N:10]2[CH2:11][CH2:12][NH:13][CH2:14][CH2:15]2)=[CH:7][CH:8]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution prepared by introducing 7.78 g (213.3 mmol) of hydrogen chloride gas in 45.9 g of ethyl acetate, 176.0 g of a solution containing the obtained (+)-1-[(4-chlorophenyl)phenylmethyl]-4-(tert-butoxycarbonyl)piperazine (optical purity 98.0% ee) was added dropwise at 20° C. over 1 hour. After stirring at that temperature, the mixture was heated up to 60° C. for 30 minutes and was stirred at this temperature for 3 hours. After cooling to 20° C., the crystals formed were collected by filtration and were washed with toluene. The crystals obtained were dried under reduced pressure to yield 8.51 g (23.7 mmol) of (+)-1-[(4-chlorophenyl)phenylmethyl]piperazine dihydrochloride from the (+)-1-[(4-chlorophenyl)phenylmethyl]-4-(tert-butoxycarbonyl)piperazine-2D-(−)-O,O′-dibenzoyltartaric acid salt in a yield of 88.1%. The optical purity of the (+)-1-[(4-chlorophenyl)phenylmethyl]piperazine in the crystals was 98.4% ee.

Workup

customTo a solution prepared
additionwas added dropwise at 20° C. over 1 hour
stirringwas stirred at this temperature for 3 hours
temperatureAfter cooling to 20° C.
customthe crystals formed
filtrationwere collected by filtration
washwere washed with toluene
customThe crystals obtained
customwere dried under reduced pressure

Sources & evidence

ORD record: ord-f85e46563e35476fab8097bec04ec912
Source dataset: uspto-grants-2004_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06803465B2

Reaction notes

Loading…