Boron tribromide → (E)-3-(4-((6-hydroxy-2-(4-hydroxyphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid

HRID 632679Notes

Reaction equation

HRID 632679 reaction equation
C[O:2][C:3]1[CH:4]=[CH:5][C:6]2[C:10]([O:11][C:12]3[CH:17]=[CH:16][C:15](/[CH:18]=[CH:19]/[C:20]([O:22]C(C)(C)C)=[O:21])=[CH:14][CH:13]=3)=[C:9]([C:27]3[CH:32]=[CH:31][C:30]([O:33]C)=[CH:29][CH:28]=3)[S:8][C:7]=2[CH:35]=1.B(Br)(Br)Br>C(Cl)Cl.CO>[OH:2][C:3]1[CH:4]=[CH:5][C:6]2[C:10]([O:11][C:12]3[CH:17]=[CH:16][C:15](/[CH:18]=[CH:19]/[C:20]([OH:22])=[O:21])=[CH:14][CH:13]=3)=[C:9]([C:27]3[CH:28]=[CH:29][C:30]([OH:33])=[CH:31][CH:32]=3)[S:8][C:7]=2[CH:35]=1

Participants

5

Reactant 2

HCID 25134Boron tribromideHCID 86730644(E)-tert-butyl 3-(4-((6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylate

Product 1

HCID 78322699(E)-3-(4-((6-hydroxy-2-(4-hydroxyphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylic acidYield 53%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (E)-tert-butyl 3-(4-((6-methoxy-2-(4-methoxyphenyl)-benzo[b]thiophen-3-yl)oxy)phenyl)acrylate (40 mg, 0.08 mmol) in DCM (2.5 mL) at 0° C. was added BBr3 (1.0 M in DCM, 0.33 mL, 0.33 mmol) dropwise, a solid immediately precipitated from the solution. The resulting mixture was stirred at 0° C. for 100 min after which the reaction was quenched by addition of sat. aq. NaHCO3 (4 mL) solution and a white precipitate was observed. The aqueous layer was then extracted with 5% MeOH/EtOAc (4×12 mL) and the combined organic layers were passed through a phase separator to remove water and concentrated in vacuo to afford the crude product which was dissolved in MeOH (2 mL) and purified by reverse phase HPLC (neutral condition, 3% 1-propanol in 1-100% CH3CN/HO) to afford (E)-3-(4-((6-hydroxy-2-(4-hydroxyphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid (17.5 mg, 0.04 mmol, 53% yield). LC/MS (m/z, MH+): 405.0790.

Workup

  1. customa solid immediately precipitated from the solution
  2. customwas quenched by addition of sat. aq. NaHCO3 (4 mL) solution
  3. extractionThe aqueous layer was then extracted with 5% MeOH/EtOAc (4×12 mL)
  4. customto remove water
  5. concentrationconcentrated in vacuo
  6. customto afford the crude product which
  7. custompurified by reverse phase HPLC (neutral condition, 3% 1-propanol in 1-100% CH3CN/HO)

Sources & evidence

ORD record
ord-393c283e4a384a5ab44bc2eab83fc6f8
Source dataset
uspto-grants-2016_04
Patent number
US09321746B2

Reaction notes

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