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

HRID 515412Notes

Reaction equation

HRID 515412 reaction equation
[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][CH:20]=3)[CH2:15][CH2:14]2)[O:10][C:9]1=[O:28])[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[CH2:17][CH2:18][CH:13]([C:11]3[O:10][C:9](=[O:28])[N:8]([CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[N:12]=3)[CH2:14][CH2:15]2)=[CH:20][CH:21]=1

Participants

4

Reactant 2

HCID 61436Stannous chloride dihydrateHCID 896511413-Benzyl-5-[1-(4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one

Product 1

HCID 896507425-[1-(4-Aminophenyl)-4-piperidyl]-3-benzyl-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 C6H5CH2Br (0.82 g, 4.8 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-(4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (6c, 1.42 g, 94%). Nitro compound (6c, 1.52 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-benzyl-2,3-dihydro-1,3,4-oxadiazol-2-one (7d, 1.23 g, 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-dimethylaminopropyl)carbodi imide)) (0.19 g, 1 mmol) and amine compound (7d, 0.35 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)piperidino]phenyl-5-nitro-2-furamide (8d, 405 mg, 83%).

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-88e48a10d5fd43dda02c57cdbb2a8913
Source dataset
uspto-grants-2015_08
Patent number
US09108960B2

Reaction notes

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