1,4-Dioxane → (E)-ethyl 3-(4-((6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophen-3-yl)amino)phenyl)acrylate

HRID 632656Notes

Reaction equation

HRID 632656 reaction equation
Br[C:2]1[C:3]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][C:4]=2[S:5][C:6]=1[C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=1.[NH2:21][C:22]1[CH:34]=[CH:33][C:25]([CH:26]=[CH:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])=[CH:24][CH:23]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>CCOC(C)=O>[CH3:20][O:19][C:16]1[CH:17]=[CH:18][C:3]2[C:2]([NH:21][C:22]3[CH:23]=[CH:24][C:25](/[CH:26]=[CH:27]/[C:28]([O:30][CH2:31][CH3:32])=[O:29])=[CH:33][CH:34]=3)=[C:6]([C:7]3[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=3)[S:5][C:4]=2[CH:15]=1

Participants

6

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 97826Ethyl 3-(4-aminophenyl)acrylateHCID 8509423-Bromo-6-methoxy-2-(4-methoxyphenyl)-benzo[b]thiophene

Product 1

HCID 86730674(E)-ethyl 3-(4-((6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophen-3-yl)amino)phenyl)acrylateYield 15%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a large microwave vial (10-20 mL) was added 3-bromo-6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene (350 mg, 1.00 mmol), ethyl 4-aminocinnamate (383 mg, 2.00 mmol) and K3PO4 (425 mg, 2.00 mmol). 1,4-dioxane (6.0 mL) was then added followed by chloro-(2-dicyclohexylphosphino-2′,6′-diisopropoxy-1,1′-biphenyl)[2-(2-aminoethyl)phenyl]palladium(II) methyl-t-butyl ether adduct (RuPhos palladacycle, 73.0 mg, 0.10 mmol) and the reaction was subjected to microwave irradiation at 120° C. for 3 h. Upon completion the reaction mixture was transferred to round bottom flask with EtOAc and concentrated in vacuo. The resulting material was partitioned between water and EtOAc and separated, the aqueous layer was then further extracted with EtOAc (3×) and the combined organic layers were passed through a phase separator to remove water and concentrated in vacuo. The crude material was purified by column chromatography (SiO2, 0-30% EtOAc/heptane) to afford (E)-ethyl 3-(4-((6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophen-3-yl)amino)phenyl)acrylate (69.0 mg, 0.15 mmol, 15% yield) as a white solid. LC/MS (m/z, MH+): 460.3.

Workup

  1. customirradiation at 120° C. for 3 h
  2. concentrationconcentrated in vacuo
  3. customThe resulting material was partitioned between water and EtOAc
  4. customseparated
  5. extractionthe aqueous layer was then further extracted with EtOAc (3×)
  6. customto remove water
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by column chromatography (SiO2, 0-30% EtOAc/heptane)

Sources & evidence

ORD record
ord-fb0d6d9979d94e5eae1bf3c946adcb49
Source dataset
uspto-grants-2016_04
Patent number
US09321746B2

Reaction notes

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