Dimethylformamide → 4-{3-[6-(3-Iodo-5-thiophen-3-yl-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy}-butyric acid ethyl ester

HRID 420366Notes

Reaction equation

HRID 420366 reaction equation
[CH2:1]([O:3][C:4](=[O:29])[CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]Br)[C:10]=1[CH2:22][CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH3:2].[I:30][C:31]1[CH:32]=[C:33]([OH:42])[CH:34]=[C:35]([C:37]2[CH:41]=[CH:40][S:39][CH:38]=2)[CH:36]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O.CC(C)=O>[CH2:1]([O:3][C:4](=[O:29])[CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][O:42][C:33]2[CH:34]=[C:35]([C:37]3[CH:41]=[CH:40][S:39][CH:38]=3)[CH:36]=[C:31]([I:30])[CH:32]=2)[C:10]=1[CH2:22][CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH3:2]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 575864914-[3-(6-Bromo-hexyl)-2-(ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl esterHCID 575865113-Iodo-5-thiophen-3-yl-phenol

Product 1

HCID 575865384-{3-[6-(3-Iodo-5-thiophen-3-yl-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy}-butyric acid ethyl esterYield 99.8%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Procedure

To a mixture of 4-[3-(6-bromo-hexyl)-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester (2.99 g, 6.35 mmol), 3-iodo-5-thiophen-3-yl-phenol (1.92 g, 6.35 mmol), and potassium carbonate (1.75 g, 12.7 mmol) were added N,N-dimethylformamide (50 mL) and acetone (100 mL) at room temperature. The resulting suspension was heated to reflux for 2 days. Then, the reaction mixture was cooled to room temperature and diluted with water (200 mL). The organic compound was extracted into ethyl acetate (3×100 mL) and the combined organic extracts were washed with water (300 mL) and brine solution (200 mL). The organic layers were dried over anhydrous magnesium sulfate and filtration of the drying agent and concentration of the solvent gave the crude product which was purified by using an ISCO 80 g column, eluting with 0-20% ethyl acetate in hexanes to afford 4-{3-[6-(3-iodo-5-thiophen-3-yl-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy}-butyric acid ethyl ester (4.39 g, 99%) as a colorless oil: ES(+)-HRMS m/e calculated for C33H41IO6S (M+Na)+ 715.1561, found 715.1561.

Workup

  1. temperatureThe resulting suspension was heated
  2. temperatureto reflux for 2 days
  3. extractionThe organic compound was extracted into ethyl acetate (3×100 mL)
  4. washthe combined organic extracts were washed with water (300 mL) and brine solution (200 mL)
  5. dry with materialThe organic layers were dried over anhydrous magnesium sulfate and filtration of the drying agent and concentration of the solvent
  6. customgave the crude product which
  7. customwas purified
  8. washeluting with 0-20% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-93f0b21dc5d54d529c952fc51a7aebd8
Source dataset
uspto-grants-2012_01
Patent number
US08093385B2

Reaction notes

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