Methyl iodide → 3-Methyl-5-[1-(4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one

HRID 515406Notes

Reaction equation

HRID 515406 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][CH:13]([C:16]3[O:20][C:19](=[O:21])[NH:18][N:17]=3)[CH2:12][CH2:11]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].CI.[C:24]([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH3:24][N:18]1[N:17]=[C:16]([CH:13]2[CH2:14][CH2:15][N:10]([C:7]3[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:9][CH:8]=3)[CH2:11][CH2:12]2)[O:20][C:19]1=[O:21]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 896504225-[1-(4-Nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one

Product 1

HCID 896506133-Methyl-5-[1-(4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-oneYield 91%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

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. customafter completion of the reaction, reaction mixture
  2. extractionextracted into chloroform finally purification by column chromatography

Sources & evidence

ORD record
ord-9ebb727f94b24eb3ae1f805bd54d56ec
Source dataset
uspto-grants-2015_08
Patent number
US09108960B2

Reaction notes

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