Piperazine → 1-(2-Fluoro-3-(trifluoromethyl)phenyl)piperazine

HRID 2358111

Reaction equation

Br[C:2]1[C:3]([F:12])=[C:4]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:6][CH:7]=1.[NH:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1.CC(C)([O-])C.[K+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].P1(O)(OC2C=CC3C(C=2C2C4C(C=CC=2O1)=CC=CC=4)=CC=CC=3)=O>[F:12][C:3]1[C:4]([C:8]([F:11])([F:10])[F:9])=[CH:5][CH:6]=[CH:7][C:2]=1[N:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 3-bromo-2-fluorobenzotrifluoride (1.72 g, 7.1 mmol) in toluene (50 ml) under nitrogen, was added piperazine (0.89 g, 10.6 mmol), potassium tert-butoxide (0.95 g, 9.9 mmol), bis(dibenzylideneacetone)palladium(0) (0.19 g, 0.21 mmol) and (+/−)-1,1′-binaphthyl-2,2′-diyl hydrogen phosphate (0.13 g, 0.21 mmol). The resulting mixture was heated at 80° C. for 20 h. Filtration through a pad of celite and evaporation of the filtrate gave 2.1 g of crude product. The residue was purified by flash column chromatography (ethylacetate/methanol, 1:1) to give the title compound (0.96 g). MS m/z (rel. intensity, 70 eV) 248 (M+, 23), 207 (10), 206 (bp), 190 (17), 163 (8).

Workup

filtrationFiltration
customthrough a pad of celite and evaporation of the filtrate
customgave 2.1 g of crude product
customThe residue was purified by flash column chromatography (ethylacetate/methanol, 1:1)

Sources & evidence

ORD record: ord-d63c18f880834a3c8157445c1ac37136
Source dataset: uspto-grants-2010_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07763639B2

Linked notes

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