Tri-tert-butylphosphine tetrafluoroborate → 1-[4-Azetidin-1-yl-2-(4,4-dimethylcyclohexyl)phenyl]-4-butylpiperazine

HRID 32177

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH2:16][CH3:17])[CH2:10][CH2:9]2)=[C:4]([CH:18]2[CH2:23][CH2:22][C:21]([CH3:25])([CH3:24])[CH2:20][CH2:19]2)[CH:3]=1.Cl.[NH:27]1[CH2:30][CH2:29][CH2:28]1.CC(C)([O-])C.[Na+].F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.O.C1(C)C(C)=CC=CC=1>[N:27]1([C:2]2[CH:7]=[CH:6][C:5]([N:8]3[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH2:16][CH3:17])[CH2:10][CH2:9]3)=[C:4]([CH:18]3[CH2:23][CH2:22][C:21]([CH3:25])([CH3:24])[CH2:20][CH2:19]3)[CH:3]=2)[CH2:30][CH2:29][CH2:28]1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 1-[4-bromo-2-(4,4-dimethylcyclohexyl)phenyl]-4-butylpiperazine (50 mg, 0.123 mmol) produced in Example (57b), azetidine hydrochloride (17 mg, 0.185 mmol), sodium t-butoxide (47 mg, 0.492 mmol), palladium(II) acetate (3 mg, 0.0123 mmol), tri-t-butylphosphonium tetrafluoroborate (11 mg, 0.0369 mmol) and xylene (1 mL) was stirred for 3 hours at an external temperature of 100° C. Water was added to the reaction mixture and extraction was performed with ethyl acetate. The separated organic layer was filtered through Celite. The solvent was distilled off by nitrogen stream to the filtrate. The resultant residue was purified by NH silica gel column chromatography (ethyl acetate/hexane) to give 1-[4-azetidin-1-yl-2-(4,4-dimethylcyclohexyl)phenyl]-4-butylpiperazine as a colorless solid.

Workup

filtrationThe separated organic layer was filtered through Celite
distillationThe solvent was distilled off by nitrogen stream to the filtrate
customThe resultant residue was purified by NH silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record: ord-33f191f7e03346e3b882e7d82f26d813
Source dataset: uspto-grants-2008_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07425554B2

Linked notes

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