5-(2-Methylpropyl)thiophene-2-carboxylic acid → 2-(4-Benzyloxy-3,5-dimethyl-phenyl)-5-(5-isobutyl-thiophen-2-yl)-[1,3,4]oxadiazole

HRID 1094310Notes

Reaction equation

HRID 1094310 reaction equation
[CH2:1]([C:5]1[S:9][C:8]([C:10]([OH:12])=O)=[CH:7][CH:6]=1)[CH:2]([CH3:4])[CH3:3].[CH2:13]([O:20][C:21]1[C:30]([CH3:31])=[CH:29][C:24]([C:25]([NH:27][NH2:28])=O)=[CH:23][C:22]=1[CH3:32])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>CCO.C1COCC1.[Pd]>[CH2:13]([O:20][C:21]1[C:22]([CH3:32])=[CH:23][C:24]([C:25]2[O:12][C:10]([C:8]3[S:9][C:5]([CH2:1][CH:2]([CH3:3])[CH3:4])=[CH:6][CH:7]=3)=[N:28][N:27]=2)=[CH:29][C:30]=1[CH3:31])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1.[CH2:1]([C:5]1[S:9][C:8]([C:10]2[O:12][C:25]([C:24]3[CH:29]=[C:30]([CH3:31])[C:21]([OH:20])=[C:22]([CH3:32])[CH:23]=3)=[N:27][N:28]=2)=[CH:7][CH:6]=1)[CH:2]([CH3:3])[CH3:4]

Participants

7

Reactant 2

HCID 196226895-(2-Methylpropyl)thiophene-2-carboxylic acidHCID 592020304-Benzyloxy-3,5-dimethylbenzoic acid hydrazide

Product 2

HCID 666369012-(4-Benzyloxy-3,5-dimethyl-phenyl)-5-(5-isobutyl-thiophen-2-yl)-[1,3,4]oxadiazoleHCID 1360299464-[5-(5-Isobutyl-thiophen-2-yl)-[1,3,4]oxadiazol-2-yl]-2,6-dimethyl-phenol

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

2-(4-Benzyloxy-3,5-dimethyl-phenyl)-5-(5-isobutyl-thiophen-2-yl)-[1,3,4]oxadiazole is prepared in analogy to Example 21 step a) and b) by coupling and cyclising 5-isobutyl-thiophene-2-carboxylic acid with 4-benzyloxy-3,5-dimethyl-benzoic acid hydrazide, LC-MS: tR=1.06 min, [M+1]+=437.17. To a solution of this compound (2.83 g, 6.75 mmol) in EtOH (50 mL) and THF (50 mL) is added Pd/C (10% Pd, 400 mg) and the slurry is stirred at rt for 48 h under 5 bar of H2. The mixture is filtered, the filtrate is concentrated and the crude product is purified by CC on silica gel eluting with heptane:EA 8:25 to give 4-[5-(5-isobutyl-thiophen-2-yl)-[1,3,4]oxadiazol-2-yl]-2,6-dimethyl-phenol (943 mg) as a white powder; LC-MS: tR=1.09 min, [M+1]+=329.36.

Workup

  1. filtrationThe mixture is filtered
  2. concentrationthe filtrate is concentrated
  3. customthe crude product is purified by CC on silica gel eluting with heptane:EA 8:25

Sources & evidence

ORD record
ord-cc18176996684e6aa3b6046f9a68eb48
Source dataset
uspto-grants-2012_03
Patent number
US08133910B2

Reaction notes

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