Triethylamine → (E)-2-(4-hydroxyphenyl)-3-(4-(2-(1-methyl-1H-imidazol-4-yl)vinyl)phenoxy)benzo[b]thiophen-6-ol

HRID 332913Notes

Reaction equation

HRID 332913 reaction equation
Br[C:2]1[CH:25]=[CH:24][C:5]([O:6][C:7]2[C:8]3[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][C:9]=3[S:10][C:11]=2[C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH:33]([C:35]1[N:36]=[CH:37][N:38]([CH3:40])[CH:39]=1)=[CH2:34]>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[OH:18][C:15]1[CH:16]=[CH:17][C:12]([C:11]2[S:10][C:9]3[CH:19]=[C:20]([OH:23])[CH:21]=[CH:22][C:8]=3[C:7]=2[O:6][C:5]2[CH:24]=[CH:25][C:2](/[CH:34]=[CH:33]/[C:35]3[N:36]=[CH:37][N:38]([CH3:40])[CH:39]=3)=[CH:3][CH:4]=2)=[CH:13][CH:14]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 120223681H-Imidazole, 4-ethenyl-1-methyl-HCID 867306533-(4-Bromophenoxy)-2-(4-hydroxyphenyl)benzo[b]thiophen-6-ol

Product 1

HCID 78324876(E)-2-(4-hydroxyphenyl)-3-(4-(2-(1-methyl-1H-imidazol-4-yl)vinyl)phenoxy)benzo[b]thiophen-6-olYield 58.2%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

To a microwave vial, 3-(4-bromophenoxy)-2-(4-hydroxyphenyl)benzo[b]thiophen-6-ol (50 mg, 0.121 mmol) was dissolved in DMF (2 ml) and triethyl amine (0.506 ml, 3.63 mmol). To the solution was added the 4-vinyl-1-methyl imidazole (39.2 mg, 0.363 mmol) and Pd(PPh3)2Cl2 (8.49 mg, 0.012 mmol). The system was flushed with nitrogen and heated at 150° C. for 1 h under microwave radiation. The mixture was cooled to room temperature and diluted with DCM and sat. NH4Cl. The organic layer was collected (phase separator) and purified by reverse phase HPLC (acidic condition, 0.1% TFA in 1-100% CH3CN/H2O) to afford (E)-2-(4-hydroxyphenyl)-3-(4-(2-(1-methyl-1H-imidazol-4-yl)vinyl)phenoxy)benzo[b]thiophen-6-ol (31 mg, 0.070 mmol, 58.2% yield) as a white solid. 1H NMR (400 MHz, CD3OD) δ ppm=3.82 (s, 3H) 6.57-6.74 (m, 3H) 6.75-6.93 (m, 3H) 6.98-7.14 (m, 3H) 7.32-7.54 (m, 5H) 8.73 (s, 1H). LC/MS (m/z, MH+): 441.3.

Workup

  1. customThe system was flushed with nitrogen
  2. temperatureThe mixture was cooled to room temperature
  3. additiondiluted with DCM and sat. NH4Cl
  4. customThe organic layer was collected (phase separator)
  5. custompurified by reverse phase HPLC (acidic condition, 0.1% TFA in 1-100% CH3CN/H2O)

Sources & evidence

ORD record
ord-71d0f1d59ea7468eb8d3270ff46942c9
Source dataset
uspto-grants-2014_11
Patent number
US08877801B2

Reaction notes

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