Dimethylcarbamoyl Chloride → 5-[1-(4-Nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one

HRID 515404Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 515404
CN(C)[C:3](Cl)=[O:4].[N+:7]([C:10]1[CH:15]=[CH:14][C:13]([N:16]2[CH2:21][CH2:20][CH:19]([C:22]([NH:24][NH2:25])=[O:23])[CH2:18][CH2:17]2)=[CH:12][CH:11]=1)([O-:9])=[O:8]>N1C=CC=CC=1>[N+:7]([C:10]1[CH:11]=[CH:12][C:13]([N:16]2[CH2:17][CH2:18][CH:19]([C:22]3[O:23][C:3](=[O:4])[NH:25][N:24]=3)[CH2:20][CH2:21]2)=[CH:14][CH:15]=1)([O-:9])=[O:8]

Komponenten

4

Edukt 2

HCID 6598Dimethylcarbamoyl ChlorideHCID 896486361-(4-Nitrophenyl)-4-piperidinecarbohydrazide

Produkt 1

HCID 896504225-[1-(4-Nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-oneAusbeute 40 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1049PyridineLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

To a stirred solution of 4-fluoro nitrobenzene (1a, 3.1 g, 22 mmol) and methyl 4-piperidine carboxylate (2, 3.15 g, 22 mmol) in DMF solvent and K2CO3 (7.6 g, 55 mmol) as base and heated at 80° C. for 10 h, after completion of the reaction, reaction is poured into ice water and extracted into ethyl acetate finally purification by column chromatography to afford pure compound methyl 1-(4-nitrophenyl)-4-piperidinecarboxy-late (3a, 4.93 g, 85%). To a stirred solution of ester (3a, 4.75 g, 18 mmol) in ethanol, NH2NH2. H2O (2.25 g, 45 mmol) is added and refluxed for 24 h. After completion of the reaction ethanol is evaporated under vacuum and water is added and extracted into ethyl acetate finally purification by column chromatography to afford pure compound 1-(4-nitrophenyl)-4-piperidinecarbohydrazide (4a, 3.99 g, 84%). Addition N,N-dimethyl carbamyl chloride (1.29 g, 12 mmol) to hydrazide (4a, 3.17 g, 12 mmol) in pyridine at room temperature (27° C.) and followed by reflux at temperature 85° C. for 2.5 h. After completion of the reaction, the reaction mixture is cooled and filtered. The residue is recrystallized from water to get 5-[1-(4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (5a, 1.39 g, 40%). Nitro compound (5a, 1.16 g, 4 mmol) on reduction with SnCl2.2H2O (2.71 g, 12 mmol) in methanol and refluxed at 65° C. for 4 h, after completion of reaction methanol is evaporated under vacuum and to this saturated sodium bicarbonate solution is added to quench the excess stannous chloride and filtered through celite bed and purified in silica column (60-120) to afforded pure compound 5-[1-(4-aminophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (7a, 884 mg, 85%). To a stirred solution of 5-nitro2-furanoic acid (0.16 g, 1 mmol) in DMF add HOBT (Hydroxybenzotriazole) (0.14 g, 1 mmol), EDCI (1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide)) (0.19 g, 1 mmol) and amine compound (7a, 0.26 g, 1 mmol) and stirred for 2 h at room temperature (27° C.), after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography using ethyl acetate-hexane (7:3) as eluant to afford pure compound N2-4-[4-(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)piperidino]phenyl-5-nitro-2-furamide (8a, 323 mg, 81%).

Aufarbeitung

  1. customAfter completion of the reaction
  2. temperaturethe reaction mixture is cooled
  3. filtrationfiltered
  4. customThe residue is recrystallized from water

Quellen und Nachweise

ORD-Eintrag
ord-469084ba7de04a14a4db88d7972717bf
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09108960B2

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