Boron tribromide → (E)-4-(4-((6-hydroxy-2-(2-isopropylphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)but-3-en-2-one

HRID 632702Notes

Reaction equation

HRID 632702 reaction equation
[CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[S:14][C:13]2[CH:15]=[C:16]([O:19]C)[CH:17]=[CH:18][C:12]=2[C:11]=1[O:21][C:22]1[CH:27]=[CH:26][C:25](/[CH:28]=[CH:29]/[C:30](=[O:32])[CH3:31])=[CH:24][CH:23]=1)([CH3:3])[CH3:2].B(Br)(Br)Br>C(Cl)Cl>[OH:19][C:16]1[CH:17]=[CH:18][C:12]2[C:11]([O:21][C:22]3[CH:23]=[CH:24][C:25](/[CH:28]=[CH:29]/[C:30](=[O:32])[CH3:31])=[CH:26][CH:27]=3)=[C:10]([C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[CH:1]([CH3:2])[CH3:3])[S:14][C:13]=2[CH:15]=1

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 118574977(E)-4-(4-((2-(2-isopropylphenyl)-6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)but-3-en-2-one

Product 1

HCID 90372224(E)-4-(4-((6-hydroxy-2-(2-isopropylphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)but-3-en-2-oneYield 16.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (E)-4-(4-((2-(2-isopropylphenyl)-6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)but-3-en-2-one (71.3 mg, 0.161 mmol) in DCM (2.5 mL) at 0° C. was added BBr3 (1.0 M in Heptane, 0.403 mL, 0.403 mmol) dropwise. The resulting mixture was stirred at 0° C. for 1 h after which time the reaction was quenched by addition of sat. aq. NaHCO3 solution and extracted with 10% i-PrOH/DCM (3×). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The crude material was purified by reverse phase HPLC (acidic condition, 0.1% TFA in 45-70% CH3CN/H2O) to afford (E)-4-(4-((6-hydroxy-2-(2-isopropylphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)but-3-en-2-one (11.1 mg, 0.026 mmol, 16%). 1H NMR (400 MHz, CD3OD) δ ppm=7.55 (d, J=16.3 Hz, 1H), 7.49 (d, J=8.8 Hz, 2H), 7.37-7.19 (m, 5H), 7.14-7.08 (m, 1H), 6.86 (d, J=8.8 Hz, 3H), 6.63 (d, J=16.3 Hz, 1H), 3.23 (p, J=6.9 Hz, 1H), 2.33 (s, 3H), 1.16 (d, J=6.8 Hz, 6H). HRMS (m/z, MH+): 429.1509.

Workup

  1. customwas quenched by addition of sat. aq. NaHCO3 solution
  2. extractionextracted with 10% i-PrOH/DCM (3×)
  3. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by reverse phase HPLC (acidic condition, 0.1% TFA in 45-70% CH3CN/H2O)

Sources & evidence

ORD record
ord-2ec01378e9f64fc9bd42735445e9ceb3
Source dataset
uspto-grants-2016_04
Patent number
US09321746B2

Reaction notes

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