Sodium hydride → (E)-ethyl 3-(4-((6-methoxy-2-(4-methoxyphenyl)-1-oxidobenzo[b]thiophen-3-yl)oxy)phenyl)-2-methylacrylate

HRID 332872Notes

Reaction equation

HRID 332872 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5](/[CH:8]=[C:9](\[CH3:15])/[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:4][CH:3]=1.[H-].[Na+].Br[C:19]1[C:20]2[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][C:21]=2[S:22](=[O:32])[C:23]=1[C:24]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=1>CN(C=O)C>[CH3:38][O:37][C:34]1[CH:35]=[CH:36][C:20]2[C:19]([O:1][C:2]3[CH:3]=[CH:4][C:5](/[CH:8]=[C:9](\[CH3:15])/[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:6][CH:7]=3)=[C:23]([C:24]3[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=3)[S:22](=[O:32])[C:21]=2[CH:33]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 14920484(E)-ethyl 3-(4-hydroxyphenyl)-2-methylacrylateHCID 159594683-Bromo-6-methoxy-2-(4-methoxyphenyl)benzothiophene 1-oxide

Product 1

HCID 86730657(E)-ethyl 3-(4-((6-methoxy-2-(4-methoxyphenyl)-1-oxidobenzo[b]thiophen-3-yl)oxy)phenyl)-2-methylacrylateYield 86%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of (E)-ethyl 3-(4-hydroxyphenyl)-2-methylacrylate (92 mg, 0.445 mmol) in DMF (2.0 mL) was added sodium hydride (60% suspension in oil, 17.79 mg, 0.445 mmol), the resulting mixture was allowed to stir for 30 min at room temperature. To the solution was added 3-bromo-6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene 1-oxide (125 mg, 0.342 mmol) as a suspension in DMF (2.0 mL). The reaction was heated to 80° C. for 15 h. Upon completion the reaction was cooled to room temperature, quenched with water and extracted with EtOAc. The combined organic layers were then washed with water, sat. aq. NaHCO3, brine and then collected (phase separator) and concentrated in vacuo to afford the crude product. The crude material was purified by column chromatography (SiO2, 0-70% EtOAc/Heptane) to afford (E)-ethyl 3-(4-((6-methoxy-2-(4-methoxyphenyl)-1-oxidobenzo[b]thiophen-3-yl)oxy)phenyl)-2-methylacrylate (144 mg, 0.294 mmol, 86% yield). LC/MS (m/z, MH+): 491.3

Workup

  1. temperatureThe reaction was heated to 80° C. for 15 h
  2. temperatureUpon completion the reaction was cooled to room temperature
  3. customquenched with water
  4. extractionextracted with EtOAc
  5. washThe combined organic layers were then washed with water, sat. aq. NaHCO3, brine
  6. customcollected (phase separator)
  7. concentrationconcentrated in vacuo
  8. customto afford the crude product
  9. customThe crude material was purified by column chromatography (SiO2, 0-70% EtOAc/Heptane)

Sources & evidence

ORD record
ord-d88c4e5bab434aa0bb673b95abdfd030
Source dataset
uspto-grants-2014_11
Patent number
US08877801B2

Reaction notes

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