3-Iodothiophene → Butyl 4-(3-thienyl)piperazine-1-carboxylate

HRID 390323

Reaction equation

[N:1]1([C:7]([O:9][C:10]([CH3:13])(C)C)=[O:8])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.I[C:15]1[CH:19]=[CH:18][S:17][CH:16]=1.[CH3:20][C:21](C)([O-])C.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>C1(C)C=CC=CC=1.O>[S:17]1[CH:18]=[CH:19][C:15]([N:4]2[CH2:3][CH2:2][N:1]([C:7]([O:9][CH2:10][CH2:13][CH2:20][CH3:21])=[O:8])[CH2:6][CH2:5]2)=[CH:16]1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of tert-butyl piperazine-1-carboxylate (0.300 g, 1.61 mmol) in 10 mL of toluene under an atmosphere of nitrogen was added 3-iodothiophene (0.390 g, 1.86 mmol), sodium tert-butoxide (0.310 g, 3.22 mmol), tris (dibenzylidenacetone)palladium (0) (0.295 g, 0.322 mmol), and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (X-Phos, 0.307 g, 0.644 mmol). The mixture was heated to 100° C. for 18 h, cooled to rt, and treated with water. The solution was extracted 3× with ethyl acetate, and the combined organic solution was washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The resultant residue was purified via silica gel chromatography, eluting with 0-70% ethyl acetate, to provide text-butyl 4-(3-thienyl)piperazine-1-carboxylate that gave a proton NMR spectra consistent with theory.

Workup

temperaturecooled to rt
extractionThe solution was extracted 3× with ethyl acetate
washthe combined organic solution was washed with brine
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe resultant residue was purified via silica gel chromatography
washeluting with 0-70% ethyl acetate

Sources & evidence

ORD record: ord-614555e96b724d83b2a7fb7b81e7bf0b
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08383638B2

Linked notes

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