Diisopropylethylamine → 3-(4-Allyloxy-2-methoxy-phenyl)-5-(4-isobutyl-5-methyl-thiophen-2-yl)-[1,2,4]oxadiazole

HRID 1676146Notes

Reaction equation

HRID 1676146 reaction equation
[CH2:1]([C:5]1[CH:6]=[C:7]([C:11]([OH:13])=O)[S:8][C:9]=1[CH3:10])[CH:2]([CH3:4])[CH3:3].[CH2:14]([O:17][C:18]1[CH:27]=[CH:26][C:21]([C:22]([NH:24]O)=[NH:23])=[C:20]([O:28][CH3:29])[CH:19]=1)[CH:15]=[CH2:16].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C.C(OCC)C>[CH2:14]([O:17][C:18]1[CH:27]=[CH:26][C:21]([C:22]2[N:23]=[C:11]([C:7]3[S:8][C:9]([CH3:10])=[C:5]([CH2:1][CH:2]([CH3:3])[CH3:4])[CH:6]=3)[O:13][N:24]=2)=[C:20]([O:28][CH3:29])[CH:19]=1)[CH:15]=[CH2:16]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 594978744-Isobutyl-5-methylthiophene-2-carboxylic acidHCID 178458445HCID 178458445, compound

Product 1

HCID 673521943-(4-Allyloxy-2-methoxy-phenyl)-5-(4-isobutyl-5-methyl-thiophen-2-yl)-[1,2,4]oxadiazoleYield 62.1%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 4-isobutyl-5-methyl-thiophene-2-carboxylic acid (505 mg, 2.55 mmol), 4-allyloxy-N-hydroxy-2-methoxy-benzamidine (611 mg, 2.75 mmol) and DIPEA (377 mg, 2.92 mmol) in DMF (10 mL) is added TBTU (882 mg, 2.75 mmol). The mixture is stirred at rt for 15 h before it is diluted with diethyl ether (100 mL) and washed with 1 N aq. NaOH (2×30 mL), 1 M aq. KHSO4 (30 mL) and brine (30 mL). The organic extract is dried (Na2SO4), filtered and evaporated. The yellow oily residue is dissolved in dry toluene (10 mL) and heated at 150° C. for 20 min in a microwave oven. The mixture is poured into diethyl ether (100 mL) and washed with brine (75 mL). The organic extract is dried (Na2SO4), filtered and evaporated to give 3-(4-allyloxy-2-methoxy-phenyl)-5-(4-isobutyl-5-methyl-thiophen-2-yl)-[1,2,4]oxadiazole (609 mg) as a yellow solid; LC-MS: tR=1.19 min, [M+1]=385.23.

Workup

  1. washwashed with 1 N aq. NaOH (2×30 mL), 1 M aq. KHSO4 (30 mL) and brine (30 mL)
  2. extractionThe organic extract
  3. dry with materialis dried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated
  6. dissolutionThe yellow oily residue is dissolved in dry toluene (10 mL)
  7. temperatureheated at 150° C. for 20 min in a microwave oven
  8. additionThe mixture is poured into diethyl ether (100 mL)
  9. washwashed with brine (75 mL)
  10. extractionThe organic extract
  11. dry with materialis dried (Na2SO4)
  12. filtrationfiltered
  13. customevaporated

Sources & evidence

ORD record
ord-87d80f81f7d94fb2891dd7873bc31f98
Source dataset
uspto-grants-2011_08
Patent number
US08003800B2

Reaction notes

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