Sodium ethoxide → 3-(1H-indol-5-yl)-5-(4-phenyl-5-(trifluoromethyl)thiophen-2-yl)-1,2,4-oxadiazole

HRID 423288Notes

Reaction equation

HRID 423288 reaction equation
[OH:1][NH:2][C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][CH:9]=[CH:8]2)=[NH:4].[C:14]1([C:20]2[CH:21]=[C:22]([C:29](OC)=O)[S:23][C:24]=2[C:25]([F:28])([F:27])[F:26])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[O-]CC.[Na+]>>[C:14]1([C:20]2[CH:21]=[C:22]([C:29]3[O:1][N:2]=[C:3]([C:5]4[CH:6]=[C:7]5[C:11](=[CH:12][CH:13]=4)[NH:10][CH:9]=[CH:8]5)[N:4]=3)[S:23][C:24]=2[C:25]([F:28])([F:26])[F:27])[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

4

Reactant 3

HCID 2723922Sodium ethoxideHCID 2781442Methyl 4-phenyl-5-(trifluoromethyl)thiophene-2-carboxylateHCID 178513238HCID 178513238, compound

Product 1

HCID 251103463-(1H-indol-5-yl)-5-(4-phenyl-5-(trifluoromethyl)thiophen-2-yl)-1,2,4-oxadiazoleYield 29.9%

Conditions

Temperature
120 °C

Procedure

D1 (174 mg) and methyl 4-phenyl-5-(trifluoromethyl)-2-thiophenecarboxylate (286 mg) were combined, treated with sodium ethoxide (21% wt in EtOH, 411 ul) and heated to 120° C. in a microwave reactor for 30 minutes. LCMS analysis showed the reaction was incomplete so microwave heating was continued for a further two periods of 30 minutes. The reaction mixture was then cooled to RT, quenched with H2O (2 ml) and evaporated to dryness under reduced pressure to give the crude product (411 mg) as a brown solid. The crude residue was purified on a 40+S Biotage cartridge, eluting with a 0 to 50% mixture of Et2O in petroleum ether. This gave the title compound (122 mg) as an off-white solid. δH (CDCl3, 400 MHz): 6.68 (1H, s), 7.30 (1H, t), 7.41-7.55 (6H, m), 7.92 (1H, s), 7.99 (1H, d), 8.36 (1H, br. s), 8.50 (1H, s). MS (ES): C21H12F3N3OS requires 411; found 410 (M−H+).

Workup

  1. temperaturewas incomplete so microwave heating
  2. customwas continued for a further two periods of 30 minutes
  3. temperatureThe reaction mixture was then cooled to RT
  4. customquenched with H2O (2 ml)
  5. customevaporated to dryness under reduced pressure
  6. customto give the crude product (411 mg) as a brown solid
  7. customThe crude residue was purified on a 40+S Biotage cartridge
  8. washeluting with a 0 to 50% mixture of Et2O in petroleum ether

Sources & evidence

ORD record
ord-a3c980443c18442f87c00fef624bc0ac
Source dataset
uspto-grants-2012_01
Patent number
US08101775B2

Reaction notes

Loading…