Dimethylformamide → 4-{2-(2-Ethoxycarbonyl-ethyl)-3-[6-(3-iodo-5-methanesulfonyl-phenoxy)-hexyl]-phenoxy}-butyric Acid Ethyl Ester

HRID 418079Notes

Reaction equation

HRID 418079 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:41])[CH:34]=[C:35]([S:37]([CH3:40])(=[O:39])=[O:38])[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:41][C:33]2[CH:34]=[C:35]([S:37]([CH3:40])(=[O:39])=[O:38])[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 578630243-Iodo-5-methanesulfonyl-phenol

Product 1

HCID 578630374-{2-(2-Ethoxycarbonyl-ethyl)-3-[6-(3-iodo-5-methanesulfonyl-phenoxy)-hexyl]-phenoxy}-butyric Acid Ethyl EsterYield 91%

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 (1.17 g, 2.49 mmol), 3-iodo-5-methanesulfonyl-phenol (620 mg, 2.08 mmol), and potassium carbonate (575 mg, 4.16 mmol) were added dimethylformamide (13.4 mL) and acetone (26.8 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 (100 mL). The organic compound was extracted into ethyl acetate (3×50 mL) and the combined organic extracts were washed with water (100 mL) and brine solution (100 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 40 g column, eluting with 2-20% ethyl acetate in hexanes to afford 4-{2-(2-ethoxycarbonyl-ethyl)-3-[6-(3-iodo-5-methanesulfonyl-phenoxy)-hexyl]-phenoxy}-butyric acid ethyl ester (1.3 g, 91%) as a colorless oil: ES(+)-HRMS m/e calcd for C30H41IO8S (M+Na)+ 711.1459, found 711.1460.

Workup

  1. temperatureThe resulting suspension was heated
  2. temperatureto reflux for 2 days
  3. extractionThe organic compound was extracted into ethyl acetate (3×50 mL)
  4. washthe combined organic extracts were washed with water (100 mL) and brine solution (100 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 2-20% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-33590f914a094992ac880d217b6435cc
Source dataset
uspto-grants-2012_01
Patent number
US08093253B2

Reaction notes

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