4-Methylmorpholine → 1-{4-[5-(2-Fluoro-biphenyl-4-yl)-[1,2,4]oxadiazol-3-yl]-benzyl}-4-(piperidine-1-ylcarbamoyl)-piperidine-4-carboxylic acid benzyl ester

HRID 2407508Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2407508
ClC(OCC(C)C)=O.[CH2:9]([O:16][C:17]([C:19]1([C:50]([OH:52])=O)[CH2:24][CH2:23][N:22]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([C:32]3[N:36]=[C:35]([C:37]4[CH:42]=[CH:41][C:40]([C:43]5[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=5)=[C:39]([F:49])[CH:38]=4)[O:34][N:33]=3)=[CH:28][CH:27]=2)[CH2:21][CH2:20]1)=[O:18])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.CN1CCOCC1.[NH2:60][N:61]1[CH2:66][CH2:65][CH2:64][CH2:63][CH2:62]1>O1CCCC1.O>[CH2:9]([O:16][C:17]([C:19]1([C:50](=[O:52])[NH:60][N:61]2[CH2:66][CH2:65][CH2:64][CH2:63][CH2:62]2)[CH2:20][CH2:21][N:22]([CH2:25][C:26]2[CH:27]=[CH:28][C:29]([C:32]3[N:36]=[C:35]([C:37]4[CH:42]=[CH:41][C:40]([C:43]5[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=5)=[C:39]([F:49])[CH:38]=4)[O:34][N:33]=3)=[CH:30][CH:31]=2)[CH2:23][CH2:24]1)=[O:18])[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Komponenten

7

Edukt 4

HCID 79724-MethylmorpholineHCID 166581-AminopiperidineHCID 62365Isobutyl chloroformateHCID 595094311-{4-[5-(2-Fluorobiphenyl-4-yl)-[1,2,4]oxadiazol-3-yl]benzyl}piperidine-4,4-dicarboxylic acid benzyl ester

Produkt 1

HCID 595094951-{4-[5-(2-Fluoro-biphenyl-4-yl)-[1,2,4]oxadiazol-3-yl]-benzyl}-4-(piperidine-1-ylcarbamoyl)-piperidine-4-carboxylic acid benzyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
5 °C

Versuchsvorschrift

Isobutyl chloroformate (0.158 mL, 0.0012 mol) is added to a solution of 1-{4-[5-(2-fluoro-biphenyl-4-yl)-[1,2,4]oxadiazol-3-yl]-benzyl}-piperidine-4,4-dicarboxylic acid benzyl ester (0.6 g, 0.0010 mol) and N-methyl morpholine (0.156 mL, 0.0015 mol) in tetrahydrofuran (20 mL) at 5° C. The reaction mixture is stirred at 5° C. for 45 minutes. 1-Amino piperidine (0.162 mL, 0.0015 mol) is added to the reaction mixture and is stirred for 30 minutes at 5° C. and then at room temperature for 45 minutes. Demineralized water (10 mL) is added to the reaction mixture, Organic layer is separated and dried over sodium sulphate. Removal of solvent under reduced pressure gives a viscous liquid, which is purified by column chromatography (silica gel 230-400 mesh, hexane:ethyl acetate 70:30) to get 1-{4-[5-(2-fluoro-biphenyl-4-yl)-[1,2,4]oxadiazol-3-yl]-benzyl}-4-(piperidine-1-ylcarbamoyl)-piperidine-4-carboxylic acid benzyl ester.

Aufarbeitung

  1. stirringis stirred for 30 minutes at 5° C.
  2. waitat room temperature for 45 minutes
  3. customis separated
  4. dry with materialdried over sodium sulphate
  5. customRemoval of solvent under reduced pressure
  6. customgives a viscous liquid, which
  7. customis purified by column chromatography (silica gel 230-400 mesh, hexane:ethyl acetate 70:30)

Quellen und Nachweise

ORD-Eintrag
ord-4964272338a64de49a43c0ee7b437a3a
Quelldatensatz
uspto-grants-2014_08
Patentnummer
US08809539B2

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