Potassium Iodide → (E)-tert-butyl 3-(4-((6-((1,1-dioxido-3-oxobenzo[d]isothiazol-2(3H)-yl)methoxy)-2-(2-isopropylphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylate

HRID 632677Notes

Reaction equation

HRID 632677 reaction equation
[OH:1][C:2]1[CH:3]=[CH:4][C:5]2[C:9]([O:10][C:11]3[CH:16]=[CH:15][C:14](/[CH:17]=[CH:18]/[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[CH:13][CH:12]=3)=[C:8]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[CH:32]([CH3:34])[CH3:33])[S:7][C:6]=2[CH:35]=1.Cl[CH2:37][N:38]1[C:42](=[O:43])[C:41]2[CH:44]=[CH:45][CH:46]=[CH:47][C:40]=2[S:39]1(=[O:49])=[O:48].C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CC(C)=O>[O:48]=[S:39]1(=[O:49])[C:40]2[CH:47]=[CH:46][CH:45]=[CH:44][C:41]=2[C:42](=[O:43])[N:38]1[CH2:37][O:1][C:2]1[CH:3]=[CH:4][C:5]2[C:9]([O:10][C:11]3[CH:12]=[CH:13][C:14](/[CH:17]=[CH:18]/[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[CH:15][CH:16]=3)=[C:8]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[CH:32]([CH3:33])[CH3:34])[S:7][C:6]=2[CH:35]=1

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 23024352-(Chloromethyl)-2,3-dihydro-1lambda6,2-benzothiazole-1,1,3-trioneHCID 118574940(E)-tert-butyl 3-(4-((6-hydroxy-2-(2-isopropylphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylate

Product 1

HCID 118574951(E)-tert-butyl 3-(4-((6-((1,1-dioxido-3-oxobenzo[d]isothiazol-2(3H)-yl)methoxy)-2-(2-isopropylphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylateYield 71%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a solution of (E)-tert-butyl 3-(4-((6-hydroxy-2-(2-isopropylphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylate (68 mg, 0.140 mmol) in acetone (2 mL) was added 2-(chloromethyl)benzo[d]isothiazol-3(2H)-one 1,1-dioxide (32.4 mg, 0.140 mmol), potassium carbonate (19.31 mg, 0.140 mmol) and potassium iodide (23.2 mg, 0.140 mmol). The resulting mixture was stirred at room temperature for 48 hours. The solvent was removed in vacuo. The resulting solid was retaken in ethyl acetate. The organic layer was washed with aqueous saturated ammonium chloride solution followed by brine. The organic layer was dried over anhydrous MgSO4 filtered and concentrated in vacuo to give the crude product, which was purified by flash chromatography (SiO2, 0-30% EtOAc/Heptane) to afford (E)-tert-butyl 3-(4-((6-((1,1-dioxido-3-oxobenzo[d]isothiazol-2(3H)-yl)methoxy)-2-(2-isopropylphenyl)benzo[b]thiophen-3-yl)oxy)phenyl)acrylate (67.4 mg, 0.099 mmol, 71% yield). 1H NMR (400 MHz, (CD3)2SO) δ 8.37 (d, J=7.4 Hz, 1H), 8.18 (dd, J=7.4, 1.3 Hz, 1H), 8.11 (td, J=7.7, 1.3 Hz, 1H), 8.04 (t, J=7.6 Hz, 1H), 7.88 (d, J=2.2 Hz, 1H), 7.61-7.54 (m, 2H), 7.48-7.34 (m, 3H), 7.34-7.30 (m, 2H), 7.23-7.15 (m, 2H), 6.89-6.81 (m, 2H), 6.33 (d, J=16.0 Hz, 1H), 5.90 (s, 2H), 3.13 (q, J=6.9 Hz, 1H), 1.45 (s, 9H), 1.13 (d, J=6.8 Hz, 6H).

Workup

  1. customThe solvent was removed in vacuo
  2. washThe organic layer was washed with aqueous saturated ammonium chloride solution
  3. dry with materialThe organic layer was dried over anhydrous MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give the crude product, which
  7. customwas purified by flash chromatography (SiO2, 0-30% EtOAc/Heptane)

Sources & evidence

ORD record
ord-3c838f1f064645168ce09cd36ff1da9c
Source dataset
uspto-grants-2016_04
Patent number
US09321746B2

Reaction notes

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