Piperidine → 1-Methyl-4-(5-((trimethylsilyl)ethynyl)pyridin-2-yl)piperazine

HRID 447446Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 447446
Br[C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.N1CCCCC1.[CH3:21][Si:22]([C:25]#[CH:26])([CH3:24])[CH3:23].CCN(CC)CC>CCOCC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[CH3:14][N:11]1[CH2:12][CH2:13][N:8]([C:5]2[CH:4]=[CH:3][C:2]([C:26]#[C:25][Si:22]([CH3:24])([CH3:23])[CH3:21])=[CH:7][N:6]=2)[CH2:9][CH2:10]1

Komponenten

8

Edukt 4

HCID 8082PiperidineHCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 164142065-Bromo-2-(4-methylpiperazin-1-yl)pyridine

Produkt 1

HCID 667304181-Methyl-4-(5-((trimethylsilyl)ethynyl)pyridin-2-yl)piperazineAusbeute 61 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418476HCID 178418476, VerbindungKatalysatorHCID 3283Diethyl EtherLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A mixture of 1-(5-bromopyridin-2-yl)-4-methylpiperazine (501.7 mg, 1.96 mmol), PdCl2(PPh3)2(51.1 mg, 0.073 mmol) and copper(I) iodide (39.9 mg, 0.21 mmol) was flushed with argon for 10 min prior to addition of piperidine (1.25 mL, 12.7 mmol) and trimethylsilylacetylene (1.40 mL, 9.9 mmol). The resulting mixture was heated at 90° C. in a sealed vial for 3 d. The reaction mixture was cooled to room temperature and the volatiles were removed in vacuo. Chromatography on Biotage (silica, SNAP-25 g, 5-15% MeOH in DCM) yielded an impure product. A second chromatography on Biotage (silica, SNAP-25 g, 0-3% Et3N in Et2O) gave 1-methyl-4-(5-((trimethylsilyl)ethynyl)pyridin-2-yl)piperazine (325.7 mg, 61%). 1H NMR (400 MHz, CDCl3) δ ppm 8.29 (d, J=1.3 Hz, 1H), 7.53 (dd, J=8.9, 2.4 Hz, 1H), 6.55 (d, J=8.8 Hz, 1H), 3.67-3.52 (m, 4H), 2.57-2.44 (m, 4H), 2.35 (s, 3H); MS ESI [M+H]+ 274.0, calcd for [C15H23N3Si+H]+ 274.2.

Aufarbeitung

  1. customwas flushed with argon for 10 min
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customthe volatiles were removed in vacuo
  4. customChromatography on Biotage (silica, SNAP-25 g, 5-15% MeOH in DCM) yielded an impure product

Quellen und Nachweise

ORD-Eintrag
ord-f5a4d3694e204932a90af4a4ce3e32fc
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08481525B2

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