Thiophenol → (R,E)-methyl 3-(4-((6-hydroxy-2-(2-(1-hydroxyethyl)phenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylate

HRID 632673Notes

Reaction equation

HRID 632673 reaction equation
[OH:1][C@@H:2]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[S:14][C:13]2[CH:15]=[C:16]([O:19]C)[CH:17]=[CH:18][C:12]=2[C:11]=1[O:21][C:22]1[CH:27]=[CH:26][C:25](/[CH:28]=[CH:29]/[C:30]([O:32][CH3:33])=[O:31])=[CH:24][CH:23]=1)[CH3:3].C1(S)C=CC=CC=1.C([O-])([O-])=O.[K+].[K+]>CCOC(C)=O>[OH:19][C:16]1[CH:17]=[CH:18][C:12]2[C:11]([O:21][C:22]3[CH:27]=[CH:26][C:25](/[CH:28]=[CH:29]/[C:30]([O:32][CH3:33])=[O:31])=[CH:24][CH:23]=3)=[C:10]([C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[C@H:2]([OH:1])[CH3:3])[S:14][C:13]=2[CH:15]=1

Participants

5

Reactant 3

HCID 7969ThiophenolHCID 11430Potassium CarbonateHCID 118574966(R,E)-methyl 3-(4-((2-(2-(1-hydroxyethyl)phenyl)-6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylate

Product 1

HCID 118574953(R,E)-methyl 3-(4-((6-hydroxy-2-(2-(1-hydroxyethyl)phenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylateYield 19%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of afford (R,E)-methyl 3-(4-((2-(2-(1-hydroxyethyl)phenyl)-6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylate (27.5 mg, 0.060 mmol) N-methyl-2-pyrrolidone (1.0 mL) was added thiophenol (0.00922 mL, 0.090 mmol) and K2CO3 (8.25 mg, 0.060 mmol). The resulting mixture was subjected to microwave irradiation at 190° C. for 1 h after which time the reaction was diluted with EtOAc and washed with brine. The layers were separated and the aqueous layer was further extracted with EtOAc, the combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The resulting crude material was purified by column chromatography (SiO2, 0-30% EtOAc/heptane) to afford (R,E)-methyl 3-(4-((6-hydroxy-2-(2-(1-hydroxyethyl)phenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylate (5 mg, 0.011, 19% yield). LC/MS (m/z, MH+): 445.0.

Workup

  1. customirradiation at 190° C. for 1 h after which time the reaction
  2. washwashed with brine
  3. customThe layers were separated
  4. extractionthe aqueous layer was further extracted with EtOAc
  5. dry with materialthe combined organic layers were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resulting crude material was purified by column chromatography (SiO2, 0-30% EtOAc/heptane)

Sources & evidence

ORD record
ord-f04729a41d6941dab2952316cde953a9
Source dataset
uspto-grants-2016_04
Patent number
US09321746B2

Reaction notes

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