Stannous chloride dihydrate → 5-[1-(4-Amino-2-fluorophenyl)-4-piperidyl]-3-benzyl-2,3-dihydro-1,3,4-oxadiazol-2-one

HRID 515421Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 515421
[CH2:1]([N:8]1[N:12]=[C:11]([CH:13]2[CH2:18][CH2:17][N:16]([C:19]3[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][C:20]=3[F:28])[CH2:15][CH2:14]2)[O:10][C:9]1=[O:29])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.O.Cl[Sn]Cl>CO>[NH2:25][C:22]1[CH:23]=[CH:24][C:19]([N:16]2[CH2:15][CH2:14][CH:13]([C:11]3[O:10][C:9](=[O:29])[N:8]([CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[N:12]=3)[CH2:18][CH2:17]2)=[C:20]([F:28])[CH:21]=1

Komponenten

4

Edukt 2

HCID 61436Stannous chloride dihydrateHCID 896510683-Benzyl-5-[1-(2-fluoro-4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one

Produkt 1

HCID 896505625-[1-(4-Amino-2-fluorophenyl)-4-piperidyl]-3-benzyl-2,3-dihydro-1,3,4-oxadiazol-2-oneAusbeute 86 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel2×

Versuchsvorschrift

5-[1-(2-Fluoro-4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (5b, 1.23 g, 4 mmol) on reacting with C6H5CH2Br (0.82 g, 1 mmol) in DMF in the presence of base K2CO3 (1.38 g, 10 mmol) at room temperature (27° C.) for 10 h, after completion of the reaction, reaction mixture is poured into ice water and extracted into chloroform finally purification by column chromatography to afford pure compound 3-benzyl-5-[1-(2-fluoro-4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (6f, 1.52 g, 96%). Nitro compound (6f, 1.59 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-amino-2-fluorophenyl)-4-piperidyl]-3-benzyl-2,3-dihydro-1,3,4-oxadiazol-2-one (7 h, 1.26 g, 86%). To a stirred solution of 5-nitro2-furanoic acid in DMF add. HOBT (Hydroxybenzotriazole) (0.14 g, 1 mmol), EDCI (1-Ethyl-3-(3-dimethyl aminopropyl)carbodi imide)) (0.19 g, 1 mmol) and amine compound (7 h, 0.36 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-(4-benzyl-5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)piperi dino]-3-fluorophenyl-5-nitro-2-furamide (8 h, 430 mg, 85%).

Aufarbeitung

  1. customis evaporated under vacuum and to this saturated sodium bicarbonate solution
  2. additionis added
  3. customto quench the excess stannous chloride
  4. filtrationfiltered through celite bed
  5. custompurified in silica column (60-120)

Quellen und Nachweise

ORD-Eintrag
ord-fdad95fd9c644466ba4637ea15bee802
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09108960B2

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