Citric Acid → (E)-methyl 3-(4-((2-bromo-6-hydroxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylate

HRID 632668Notes

Reaction equation

HRID 632668 reaction equation
[Br:1][C:2]1[S:6][C:5]2[CH:7]=[C:8]([O:11]C)[CH:9]=[CH:10][C:4]=2[C:3]=1[O:13][C:14]1[CH:19]=[CH:18][C:17](/[CH:20]=[CH:21]/[C:22]([O:24][CH3:25])=[O:23])=[CH:16][CH:15]=1.B(Br)(Br)Br.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.P([O-])([O-])([O-])=O.[Na+].[Na+].[Na+]>C(Cl)Cl>[Br:1][C:2]1[S:6][C:5]2[CH:7]=[C:8]([OH:11])[CH:9]=[CH:10][C:4]=2[C:3]=1[O:13][C:14]1[CH:15]=[CH:16][C:17](/[CH:20]=[CH:21]/[C:22]([O:24][CH3:25])=[O:23])=[CH:18][CH:19]=1.[Br:1][C:2]1[S:6][C:5]2[CH:7]=[C:8]([OH:11])[CH:9]=[CH:10][C:4]=2[C:3]=1[O:13][C:14]1[CH:15]=[CH:16][C:17](/[CH:20]=[CH:21]/[C:22]([OH:24])=[O:23])=[CH:18][CH:19]=1

Participants

7

Reactant 4

HCID 311Citric AcidHCID 24243Trisodium PhosphateHCID 25134Boron tribromideHCID 118574969(E)-methyl 3-(4-((2-bromo-6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylate

Product 2

HCID 118574926(2E)-3-[4-[(2-Bromo-6-hydroxybenzo[b]thien-3-yl)oxy]phenyl]-2-propenoic acidYield 17%HCID 118574972(E)-methyl 3-(4-((2-bromo-6-hydroxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylateYield 69%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of (E)-methyl 3-(4-((2-bromo-6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylate (2.4 g, 5.72 mmol) in DCM (20 mL) at room temperature was added BBr3 (1.0 M in Heptane, 17.17 mL, 17.17 mmol) dropwise. The resulting mixture was stirred at room temperature for 2 h after which time an aqueous buffer (pH 7.4, made from citric acid and dibasic sodium phosphate, 10 mL), cooled to 0° C. was slowly added into the reaction. The resulting mixture was then diluted with DCM (30 mL) and stirred at room temperature for 1 h. The phases were then separated and the organic phase was dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The crude material was purified by column chromatography (SiO2, 0-100% EtOAc/Heptane) to afford (E)-methyl 3-(4-((2-bromo-6-hydroxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylate (1.6 g, 3.95 mmol, 69% yield) as a pale yellow solid and (E)-3-(4-((2-bromo-6-hydroxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid (370 mg, 0.946 mmol, 17% yield) as a yellow solid.

Workup

  1. additionwas slowly added into the reaction
  2. customThe phases were then separated
  3. dry with materialthe organic phase was dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by column chromatography (SiO2, 0-100% EtOAc/Heptane)

Sources & evidence

ORD record
ord-4804094636004c09809a6743ecd719a4
Source dataset
uspto-grants-2016_04
Patent number
US09321746B2

Reaction notes

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