Stannous chloride dihydrate → 5-[1-(4-Aminophenyl)-4-piperidyl]-3-methyl-2,3-dihydro-1,3,4-oxadiazol-2-one

HRID 515407Notes

Reaction equation

HRID 515407 reaction equation
[CH3:1][N:2]1[N:6]=[C:5]([CH:7]2[CH2:12][CH2:11][N:10]([C:13]3[CH:18]=[CH:17][C:16]([N+:19]([O-])=O)=[CH:15][CH:14]=3)[CH2:9][CH2:8]2)[O:4][C:3]1=[O:22].O.O.Cl[Sn]Cl>CO>[NH2:19][C:16]1[CH:15]=[CH:14][C:13]([N:10]2[CH2:9][CH2:8][CH:7]([C:5]3[O:4][C:3](=[O:22])[N:2]([CH3:1])[N:6]=3)[CH2:12][CH2:11]2)=[CH:18][CH:17]=1

Participants

4

Reactant 2

HCID 61436Stannous chloride dihydrateHCID 896506133-Methyl-5-[1-(4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one

Product 1

HCID 896484465-[1-(4-Aminophenyl)-4-piperidyl]-3-methyl-2,3-dihydro-1,3,4-oxadiazol-2-oneYield 88%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

5-[1-(4-Nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (5a, 1.16 g, 4 mmol) on reacting with CH3I (0.68g, 4.8 mmol) in DMF in the presence of base K2CO3 (1.38 g, 10 mmol) at 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-methyl-5-[1-(4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (6a, 1.10 g, 91%). Nitro compound (6a, 1.21 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]-3-methyl-2,3-dihydro-1,3,4-oxadiazol-2-one (7b, 960 mg, 88%). To a stirred solution of 5-nitro2-furanoic acid in DMF add HOBT (Hydroxybenzotriazole) (0.14 g, 1 mmol), EDCI (1-Ethyl-3-(3-dimethylamino propyl)carbodi imide)) (0.19 g, 1 mmol) and amine compound (7b, 0.27 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-methyl-5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)piperidino]phenyl-5-nitro-2-furamide (8b, 351 mg, 85%).

Workup

  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)

Sources & evidence

ORD record
ord-041cc4c991924f82872e8391fa76d00c
Source dataset
uspto-grants-2015_08
Patent number
US09108960B2

Reaction notes

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