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

HRID 515419Notes

Reaction equation

HRID 515419 reaction equation
[CH2:1]([N:3]1[N:7]=[C:6]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]3[CH:19]=[CH:18][C:17]([N+:20]([O-])=O)=[CH:16][C:15]=3[F:23])[CH2:10][CH2:9]2)[O:5][C:4]1=[O:24])[CH3:2].O.O.Cl[Sn]Cl>CO>[NH2:20][C:17]1[CH:18]=[CH:19][C:14]([N:11]2[CH2:12][CH2:13][CH:8]([C:6]3[O:5][C:4](=[O:24])[N:3]([CH2:1][CH3:2])[N:7]=3)[CH2:9][CH2:10]2)=[C:15]([F:23])[CH:16]=1

Participants

4

Reactant 2

HCID 61436Stannous chloride dihydrateHCID 896511653-Ethyl-5-[1-(2-fluoro-4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one

Product 1

HCID 896482695-[1-(4-Amino-2-fluorophenyl)-4-piperidyl]-3-ethyl-2,3-dihydro-1,3,4-oxadiazol-2-oneYield 571.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

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 C2H5Br (0.53 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-ethyl-5-[1-(2-fluoro-4-nitrophenyl)-4-piperidyl]-2,3-dihydro-1,3,4-oxadiazol-2-one (6e, 1.27 g, 95%). Nitro compound (6e, 1.34 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-ethyl-2,3-dihydro-1,3,4-oxadiazol-2-one (7 g, 1.05 g, 86%). To a stirred solution of 5-nitro2-furanoic acid in DMF add HOBT (Hydroxybenzo triazole) (0.14 g, 1 mmol), EDCI (1-Ethyl-3-(3-dimethylaminopropyl)carbodi imide)) (0.19 g, 1 mmol) and amine compound (7g, 0.3 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-ethyl-5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)piperidino]-3-fluorophenyl-5-nitro-2-furamide (8 g, 391 mg, 88%).

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-fd76c50602c147c78cfe0a54fd282d2d
Source dataset
uspto-grants-2015_08
Patent number
US09108960B2

Reaction notes

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