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

HRID 632690Notes

Reaction equation

HRID 632690 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]=[C:19](\[CH3:25])/[C:20]([O:22]CC)=[O:21])=[CH:14][CH:13]=3)=[C:9]([C:26]3[CH:31]=[CH:30][C:29]([O:32]C)=[CH:28][CH:27]=3)[S:8][C:7]=2[CH:34]=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:13]=[CH:14][C:15](/[CH:18]=[C:19](\[CH3:25])/[C:20]([OH:22])=[O:21])=[CH:16][CH:17]=3)=[C:9]([C:26]3[CH:27]=[CH:28][C:29]([OH:32])=[CH:30][CH:31]=3)[S:8][C:7]=2[CH:34]=1

Participants

5

Reactant 2

HCID 25134Boron tribromideHCID 86730660(E)-ethyl 3-(4-((6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)-2-methylacrylate

Product 1

HCID 78322701(E)-3-(4-((6-hydroxy-2-(4-hydroxyphenyl)-benzo[b]thiophen-3-yl)oxy)phenyl)-2-methylacrylic acidYield 34.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (E)-ethyl 3-(4-((6-methoxy-2-(4-methoxyphenyl)-benzo[b]thiophen-3-yl)oxy)phenyl)-2-methylacrylate (107 mg, 0.225 mmol) in DCM (5.0 mL) at 0° C. was added BBr3 (1.0 M in DCM, 0.902 mL, 0.902 mmol) dropwise. 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) and acidified to pH 3 by addition of concentrated HCl. 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 and purified by reverse phase HPLC (neutral condition, 3% 1-propanol in 1-100% CH3CN/H2O) to afford (E)-3-(4-((6-hydroxy-2-(4-hydroxyphenyl)-benzo[b]thiophen-3-yl)oxy)phenyl)-2-methylacrylic acid (32.4 mg, 0.078 mmol, 34% yield). HRMS (m/z, MH+): 419.0872.

Workup

  1. customwas quenched by addition of sat. aq. NaHCO3 (4 mL)
  2. additionacidified to pH 3 by addition of concentrated HCl
  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/H2O)

Sources & evidence

ORD record
ord-b95480ec88544ccd81e7bd5d7aee027d
Source dataset
uspto-grants-2016_04
Patent number
US09321746B2

Reaction notes

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