Potassium Cyanide → 5-(3-Chlorothiophen-2-yl)-3-(4-chloro-3-cyano-phenyl)-[1,2,4]-oxadiazole

HRID 2250462Notes

Reaction equation

HRID 2250462 reaction equation
N([O-])=O.[Na+].N[C:6]1[CH:7]=[C:8]([C:13]2[N:17]=[C:16]([C:18]3[S:19][CH:20]=[CH:21][C:22]=3[Cl:23])[O:15][N:14]=2)[CH:9]=[CH:10][C:11]=1[Cl:12].[C-:24]#[N:25].[K+].C(=O)([O-])[O-].[Na+].[Na+]>S(=O)(=O)(O)O.O.C(OCC)(=O)C>[Cl:23][C:22]1[CH:21]=[CH:20][S:19][C:18]=1[C:16]1[O:15][N:14]=[C:13]([C:8]2[CH:9]=[CH:10][C:11]([Cl:12])=[C:6]([C:24]#[N:25])[CH:7]=2)[N:17]=1

Participants

8

Reactant 4

HCID 9032Potassium CyanideHCID 10340Sodium CarbonateHCID 99956372-Chloro-5-[5-(3-chlorothiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-phenylamineHCID 23668193Sodium Nitrite

Product 1

HCID 103587325-(3-Chlorothiophen-2-yl)-3-(4-chloro-3-cyano-phenyl)-[1,2,4]-oxadiazoleYield 22%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent3×HCID 1118Sulfuric AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of sodium nitrite (76.8 mg, 1.11 mmol) and water (650 μL) was added dropwise to a stirred suspension of 3-(3-amino-4-chloro-phenyl)-5-(3-chlorothiophen-2-yl)-[1,2,4]-oxadiazole (335 mg, 1.07 mmol) in sulfuric acid (3.0 mL), water (8 mL) and some crushed ice in an ice bath. The solution was stirred for 1.25 h and then was poured into a solution of cuprous cyanide (152 mg, 1.70 mmol), potassium cyanide (231 mg, 3.55 mmol) and water (8 mL) in an ice bath. The solution was stirred for 10 min, then ethyl acetate (50 mL) was added, followed by sodium carbonate to bring the solution to pH 7, and the solution was equilibrated to room temperature. The ethyl acetate layer was concentrated by rotary evaporation and the product was purified by column chromatography to yield 75.7 mg (22%) of the title compound as a light yellow solid. 1H NMR (CDCl3): 8.49 (d, J=2.20 Hz, 1H), 8.33 (dd, J1=8.52 Hz, J2=2.20 Hz, 1H), 7.67 (m, 2H), 7.16 (d, J=5.50 Hz, 1H).

Workup

  1. stirringThe solution was stirred for 10 min
  2. customwas equilibrated to room temperature
  3. concentrationThe ethyl acetate layer was concentrated by rotary evaporation
  4. customthe product was purified by column chromatography

Sources & evidence

ORD record
ord-d84e9bb5aae9424b8f13c7117f460653
Source dataset
uspto-grants-2008_01
Patent number
US07317029B2

Reaction notes

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