Dimethyl Sulfoxide → 1-[5-(Ethyloxy)-2-methyl-4-nitrophenyl]-4-[2-(methylsulfonyl)ethyl]piperidine

HRID 419627Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 419627
[CH3:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[C:5]([O:11][CH2:12][CH3:13])=[CH:4][C:3]=1F.Cl.[CH3:16][S:17]([CH2:20][CH2:21][CH:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)(=[O:19])=[O:18].C([O-])([O-])=O.[K+].[K+].CS(C)=O>CCOC(C)=O.C(Cl)Cl>[CH2:12]([O:11][C:5]1[C:6]([N+:8]([O-:10])=[O:9])=[CH:7][C:2]([CH3:1])=[C:3]([N:25]2[CH2:26][CH2:27][CH:22]([CH2:21][CH2:20][S:17]([CH3:16])(=[O:19])=[O:18])[CH2:23][CH2:24]2)[CH:4]=1)[CH3:13]

Komponenten

7

Edukt 4

HCID 679Dimethyl SulfoxideHCID 11430Potassium CarbonateHCID 594528831-Ethoxy-5-fluoro-4-methyl-2-nitrobenzeneHCID 666497114-(2-Methanesulfonylethyl)piperidine hydrochloride

Produkt 1

HCID 594525651-[5-(Ethyloxy)-2-methyl-4-nitrophenyl]-4-[2-(methylsulfonyl)ethyl]piperidineAusbeute 66,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To 1-(ethyloxy)-5-fluoro-4-methyl-2-nitrobenzene (Example 215, step A) (13.1 g, 65.9 mmol), 4-[2-(methylsulfonyl)ethyl]piperidine hydrochloride (15.0 g, 65.9 mmol) and K2CO3 (31.9 g, 231 mmol) was added DMSO (300 mL). The reaction mixture was heated at 100° C. overnight. The reaction was cooled to rt and diluted with EtOAc and DCM. The organic layer was washed with H2O and the aqueous layer was backextracted with DCM. The combined organic layers were dried (MgSO4), filtered and rotovapped down. Purification by flash chromatography provided the title compound of Step F (16.2 g, 43.6 mmol, 66% yield). This reaction was carried out in duplicate to provide an overall amount of 33.2 g, 89.4 mmol of the title compound of Step F. 1H NMR (400 MHz, DMSO-d6) δ 7.79 (s, 1H), 6.56-6.73 (m, 1H), 4.16 (q, J=7.0 Hz, 2H), 3.30 (d, J=12.2 Hz, 2H), 3.04-3.15 (m, 2H), 2.95 (s, 3H), 2.74 (t, J=11.5 Hz, 2H), 2.26 (s, 3H), 1.81-1.97 (m, 4H), 1.42-1.74 (m, 6H).

Aufarbeitung

  1. temperatureThe reaction was cooled to rt
  2. washThe organic layer was washed with H2O
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. filtrationfiltered
  5. customPurification by flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-406f3a43664b4e0c9ec7227c32d19847
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08093239B2

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