Dimethylformamide → tert-Butyl4-[5-(trifluoromethyl)pyridin-3-yl]piperazine-1-carboxylate

HRID 270550Notes

Reaction equation

[F-].[K+].IC1[CH:5]=[C:6]([N:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]2)[CH:7]=[CH:8][CH:9]=1.[F:23][C:24]([Si](C)(C)C)([F:26])[F:25].C[N:32](C=O)C>CCOC(C)=O.[Cu]I>[F:23][C:24]([F:26])([F:25])[C:8]1[CH:7]=[C:6]([N:10]2[CH2:11][CH2:12][N:13]([C:16]([O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:17])[CH2:14][CH2:15]2)[CH:5]=[N:32][CH:9]=1

Participants

Conditions

Temperature: 50 °C

Procedure

Copper(I) iodide (0.49 g, 2.6 mmol) and potassium fluoride (0.15 g, 2.6 mmol) in a flask were flame-heated under gentle shaking and at high vacuum until a greenish color appeared. A solution of tert-butyl 4-(3-iodophenyl)piperazine-1-carboxylate (0.5 g, 1.0 mmol) and (trifluoromethyl)trimethylsilane (0.37 g, 2.6 mmol) in DMF (5 mL) was added. The brown solution was stirred at room temperature overnight. More (trifluoromethyl)trimethylsilane (0.37 g) was added. The mixture was heated at 50° C. overnight, diluted with EtOAc and washed with saturated ammonium chloride. The aqueous layer was extracted with EtOAc three times. The combined organic layers were dried (MgSO4), concentrated and purified by flash chromatography on silica gel (20% to 40% EtOAc/hexanes) to give 120 mg of desired product. MS calculated for C15H20F3N3O2: (M+H) 332; found 332.1.

Workup

stirringThe brown solution was stirred at room temperature overnight
washwashed with saturated ammonium chloride
extractionThe aqueous layer was extracted with EtOAc three times
dry with materialThe combined organic layers were dried (MgSO4)
concentrationconcentrated
custompurified by flash chromatography on silica gel (20% to 40% EtOAc/hexanes)

Sources & evidence

ORD record: ord-83f366f563e345479bc29eb6eb004099
Source dataset: uspto-grants-2008_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07449467B2

Reaction notes

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