Oxalyl chloride → 3-[4-(Carbomethoxy)phenyl]-5-(4-phenyl-5-trifluoromethyl-2-thienyl)-1,2,4-oxadiazole

HRID 1454329Notes

Reaction equation

HRID 1454329 reaction equation
[C:1]1([C:7]2[CH:8]=[C:9]([C:16]([OH:18])=O)[S:10][C:11]=2[C:12]([F:15])([F:14])[F:13])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(Cl)(=O)C(Cl)=O.[C:25]([C:29]1[CH:38]=[CH:37][C:32]([C:33](=[N:35]O)[NH2:34])=[CH:31][CH:30]=1)([O:27][CH3:28])=[O:26]>C(Cl)Cl.CN(C=O)C>[C:25]([C:29]1[CH:38]=[CH:37][C:32]([C:33]2[N:34]=[C:16]([C:9]3[S:10][C:11]([C:12]([F:13])([F:14])[F:15])=[C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[CH:8]=3)[O:18][N:35]=2)=[CH:31][CH:30]=1)([O:27][CH3:28])=[O:26]

Participants

6

Reactant 3

HCID 65578Oxalyl chlorideHCID 27833724-Phenyl-5-(trifluoromethyl)thiophene-2-carboxylic acidHCID 6815810methyl 4-(N-hydroxycarbamimidoyl)benzoate

Product 1

HCID 113278703-[4-(Carbomethoxy)phenyl]-5-(4-phenyl-5-trifluoromethyl-2-thienyl)-1,2,4-oxadiazoleYield 65.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of 408 mg (1.5 mmol) of 4-phenyl-5-trifluoromethyl-thiophene-2-carboxylic acid and 1 mL of oxalyl chloride in 5 mL of CH2Cl2 was treated with 5 drops of DMF. The resulting mixture was stirred at rt for 1 h, then concentrated. The crude acid chloride and 291 mg (1.5 mmol) of 4-(carbomethoxy)benzamidoxime were dissolved in 7 mL of 6:1 v/v xylenes/pyridine. The resulting solution was heated at 140° C. for 1 h, then cooled. The mixture was partitioned between 50 mL of 1:1 EtOAc/ether and 50 mL of 1 N HCl. The organic layer was separated, washed with 3×50 mL of 1 N HCl, 50 mL of sat'd NaHCO3, dried and concentrated. Chromatography on a Biotage 40 M cartridge using hexanes (1L), then 20:1 v/v hexanes/EtOAc (1 L) as the eluant afforded 423 mg (65%) of the title compound: 1H NMR (500 Mhz) δ0 3.97 (s, 3H), 7.48 (app s, 5H), 7.92 (s, 1H), 8.18 (app d, J=8.5, 2H), 8.23 (app d, J=8.5, 2H).

Workup

  1. concentrationconcentrated
  2. temperatureThe resulting solution was heated at 140° C. for 1 h
  3. temperaturecooled
  4. customThe mixture was partitioned between 50 mL of 1:1 EtOAc/ether and 50 mL of 1 N HCl
  5. customThe organic layer was separated
  6. washwashed with 3×50 mL of 1 N HCl, 50 mL of sat'd NaHCO3
  7. customdried
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-17326924a80e4478a269c9811c29c306
Source dataset
uspto-grants-2009_01
Patent number
US07479504B2

Reaction notes

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