Trifluoroacetic acid → (E)-3-(4-((6-acetoxy-2-(2-isopropylphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid

HRID 632706Notes

Reaction equation

HRID 632706 reaction equation
[C:1]([O:4][C:5]1[CH:6]=[CH:7][C:8]2[C:12]([O:13][C:14]3[CH:19]=[CH:18][C:17](/[CH:20]=[CH:21]/[C:22]([O:24]C(C)(C)C)=[O:23])=[CH:16][CH:15]=3)=[C:11]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[CH:35]([CH3:37])[CH3:36])[S:10][C:9]=2[CH:38]=1)(=[O:3])[CH3:2].C(O)(C(F)(F)F)=O>C(Cl)Cl.CO>[C:1]([O:4][C:5]1[CH:6]=[CH:7][C:8]2[C:12]([O:13][C:14]3[CH:15]=[CH:16][C:17](/[CH:20]=[CH:21]/[C:22]([OH:24])=[O:23])=[CH:18][CH:19]=3)=[C:11]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[CH:35]([CH3:36])[CH3:37])[S:10][C:9]=2[CH:38]=1)(=[O:3])[CH3:2]

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 118574941(E)-tert-butyl 3-(4-((6-acetoxy-2-(2-isopropylphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylate

Product 1

HCID 90350325(E)-3-(4-((6-acetoxy-2-(2-isopropylphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylic acidYield 67.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of (E)-tert-butyl 3-(4-((6-acetoxy-2-(2-isopropylphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylate (65 mg, 0.123 mmol) in DCM (3.0 mL) at 0° C. was added TFA dropwise over 5 min. The reaction was stirred at 0° C. for 1 h after which time it was warmed to room temperature for an additional 55 min. The mixture was then diluted with DCM and concentrated in vacuo to remove both DCM and TFA. The crude material was then further azeotroped with DCM (3×) to make sure all of the TFA was removed and gave a pale yellow solid. The resulting crude material was dissolved in MeOH (3 mL) and purified by reverse phase HPLC (acidic conditions, 0.1% TFA in 45-70% CH3CN/H2O) to afford (E)-3-(4-((6-acetoxy-2-(2-isopropylphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylic acid (39.1 mg, 0.083 mmol, 67% yield). 1H NMR (400 MHz, CD3OD) δ ppm=7.69 (d, J=2.0 Hz, 11), 7.57 (d, J=15.9 Hz, 1H), 7.45 (dd, J=8.7, 6.4 Hz, 3H), 7.40-7.26 (m, 3H), 7.18-7.10 (m, 2H), 6.86 (d, J=8.8 Hz, 2H), 6.32 (d, J=16.0 Hz, 1H), 3.20 (p, J=6.9 Hz, 1H), 2.32 (s, 3H), 1.17 (d, J=6.9 Hz, 6H). HRMS (m/z, MH+): 473.1399.

Workup

  1. temperaturewas warmed to room temperature for an additional 55 min
  2. concentrationconcentrated in vacuo
  3. customto remove both DCM and TFA
  4. customThe crude material was then further azeotroped with DCM (3×)
  5. customwas removed
  6. customgave a pale yellow solid
  7. custompurified by reverse phase HPLC (acidic conditions, 0.1% TFA in 45-70% CH3CN/H2O)

Sources & evidence

ORD record
ord-500a7ce5fac44eb1ac587ac7819a8d61
Source dataset
uspto-grants-2016_04
Patent number
US09321746B2

Reaction notes

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