Citric Acid → 1-(tert-Butoxycarbonyl)-4-(4-chlorobenzoylmethanesulfonyl)piperazine

HRID 278577Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([S:14]([CH3:17])(=[O:16])=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.[Cl:23][C:24]1[CH:33]=[CH:32][C:27]([C:28](OC)=[O:29])=[CH:26][CH:25]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1.CCCCCC.O>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([S:14]([CH2:17][C:28](=[O:29])[C:27]2[CH:32]=[CH:33][C:24]([Cl:23])=[CH:25][CH:26]=2)(=[O:15])=[O:16])[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 1-(tert-butoxycarbonyl)-4-methanesulfonylpiperazine (1.32 g) in tetrahydrofurane (10 ml) was added dropwise at 0° C. 1.6 M n-butyllithium in hexane (6.25 ml), and the mixture was stirred at room temperature for 30 minutes. The reaction solution was cooled to −78° C., and to the mixture was added a solution of methyl 4-chlorobenzoate (853 mg) in tetrahydrofurane (5 ml). The mixture was stirred for 3 hours at the same temperature and raised to 0° C. To the reaction solution was added water (10 ml), and the mixture was made acidic with citric acid aqueous solution and extracted with ether. The organic layer was washed with brine, dried, concentrated, and purified with silica gel column chromatography (hexane/ethyl acetate=2/1) to give a colorless solid of the title compound (790 mg).

Workup

temperatureraised to 0° C
extractionextracted with ether
washThe organic layer was washed with brine
customdried
concentrationconcentrated
custompurified with silica gel column chromatography (hexane/ethyl acetate=2/1)

Sources & evidence

ORD record: ord-b2cc35848a47496aa0f74711eea76541
Source dataset: uspto-grants-2002_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06359134B1

Reaction notes

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