3,4-Diethoxybenzoic acid → 5-(3,4-Diethoxyphenyl)-3-(1H-indol-4-yl)-1,2,4-oxadiazole

HRID 710371Notes

Reaction equation

HRID 710371 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][C:12]=1[O:13][CH2:14][CH3:15])[C:7]([OH:9])=O)[CH3:2].O[NH:17][C:18]([C:20]1[C:21]2[CH:22]=[CH:23][NH:24][C:25]=2[CH:26]=[CH:27][CH:28]=1)=[NH:19].C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C1COCC1.CCOC(C)=O>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:7]2[O:9][N:19]=[C:18]([C:20]3[CH:28]=[CH:27][CH:26]=[C:25]4[C:21]=3[CH:22]=[CH:23][NH:24]4)[N:17]=2)[CH:10]=[CH:11][C:12]=1[O:13][CH2:14][CH3:15])[CH3:2]

Participants

7

Reactant 4

HCID 794173,4-Diethoxybenzoic acidHCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 178513279HCID 178513279, compound

Product 1

HCID 251102975-(3,4-Diethoxyphenyl)-3-(1H-indol-4-yl)-1,2,4-oxadiazoleYield 34%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3,4-diethoxybenzoic acid (0.11 g; 0.52 mmol), and the product of Step A (0.09 g; 0.51 mmol) in anhydrous THF (2 ml), PyBroP (0.25 g; 0.54 mmol) was added followed by DIPEA (0.21 ml; 1.22 mmol), with stirring, at room temperature under N2. After 2 h of stirring, the mixture was diluted to 15 ml with EtOAc, washed with saturated NH4Cl (2×5 ml), brine, dried over anhydrous MgSO4 and filtered. The filtrate was evaporated to dryness under reduced pressure and the residue was suspended in anhydrous toluene (10 ml). To it 1M TBAF in THF (0.5 ml) was added and the reaction mixture was refluxed for 3 h under N2, cooled to room temperature and solvents were removed under reduced pressure. The residue was washed with H2O (5 ml) and the solid was purified by FCC (SiO2; CH2Cl2) to give the title compound (0.06 g; 34%) as colourless solid. 1H-NMR (CDCl3) 1.5 (m, 6H); 4.16-4.26 (m, 4H); 6.98 (d, 1H, J=8.5 Hz), 7.31-7.37 (m, 3H); 7.54 (d, 1H, J=8.1 Hz); 7.74 (d, 1H, J=2 Hz); 7.83 (d, 1H, J=8.4 Hz); 8.06 (dd, 1H, J=2, 8.4 Hz); 8.42 (s, 1H).

Workup

  1. stirringAfter 2 h of stirring
  2. washwashed with saturated NH4Cl (2×5 ml), brine
  3. dry with materialdried over anhydrous MgSO4
  4. filtrationfiltered
  5. customThe filtrate was evaporated to dryness under reduced pressure
  6. additionTo it 1M TBAF in THF (0.5 ml) was added
  7. temperaturethe reaction mixture was refluxed for 3 h under N2
  8. temperaturecooled to room temperature
  9. customsolvents were removed under reduced pressure
  10. washThe residue was washed with H2O (5 ml)
  11. customthe solid was purified by FCC (SiO2; CH2Cl2)

Sources & evidence

ORD record
ord-9a5628ef51e54fbc8e81acc47ac38617
Source dataset
uspto-grants-2015_11
Patent number
US09181182B2

Reaction notes

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