Acetic Acid → {2-Ethyl-4-[({2-methyl-5-[4-(trifluoromethyl)phenyl]-3-furyl}methyl)thio]phenoxy}acetic acid

HRID 9692

Reaction equation

HRID 9692 reaction equation
C(O)(=O)C.C([O:7][C:8](=[O:23])[CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([S:17](Cl)(=O)=O)=[CH:13][C:12]=1[CH2:21][CH3:22])C.Cl[Si](Cl)(C)C.[CH3:29][C:30]1[O:31][C:32]([C:37]2[CH:42]=[CH:41][C:40]([C:43]([F:46])([F:45])[F:44])=[CH:39][CH:38]=2)=[CH:33][C:34]=1[CH2:35]O>C(OCC)(=O)C.[Zn]>[CH2:21]([C:12]1[CH:13]=[C:14]([S:17][CH2:35][C:34]2[CH:33]=[C:32]([C:37]3[CH:38]=[CH:39][C:40]([C:43]([F:46])([F:44])[F:45])=[CH:41][CH:42]=3)[O:31][C:30]=2[CH3:29])[CH:15]=[CH:16][C:11]=1[O:10][CH2:9][C:8]([OH:7])=[O:23])[CH3:22]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 6398DichlorodimethylsilaneHCID 21986343Ethyl 2-(4-(chlorosulfonyl)-2-ethylphenoxy)acetate2×HCID 21986436[2-Methyl-5-(4-trifluoromethyl-phenyl)-furan-3-yl]-methanol

Product 1

HCID 10225846{2-Ethyl-4-[({2-methyl-5-[4-(trifluoromethyl)phenyl]-3-furyl}methyl)thio]phenoxy}acetic acid

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8857Ethyl AcetateSolvent3×

Conditions

Temperature
60 °C

Procedure

To a mixture of zinc (407 mg) in ethyl acetate (10 ml) stirred at 60° C. was added acetic acid (0.203 ml) followed by a solution of ethyl[4-(chlorosulfonyl)-2-ethylphenoxy]acetate (intermediate 111, 546 mg) in ethyl acetate. The reaction mixture was stirred 60° C. for 2 hours and then dichlorodimethylsilane (0.431 ml) was added drop-wise. After a further 90 minutes {2-methyl-5-[4-(trifluoromethyl)phenyl]-3-furyl}methanol (472 mg) was added and the reaction mixture stirred at reflux for 17 hours. The reaction mixture was diluted with ethyl acetate; extracted with water, saturated aqueous sodium bicarbonate, water and dried with brine and over sodium sulfate. An attempt was purify the crude material by Biotage® chromatography using 3:2 petroleum ether: ethyl acetate as eluent. The partially purified material (223 mg) was hydrolyzed in 1,4-dioxan (6 ml) using 0.5 M aqueous sodium hydroxide (1.86 ml) for 16 hours. The reaction mixture was neutralized with 50W×2-200 Dowex; evaporated and the residue purified by mass-directed autopreparative HPLC to give the title compound as a solid.

Workup

  1. stirringThe reaction mixture was stirred 60° C. for 2 hours
  2. stirringthe reaction mixture stirred
  3. temperatureat reflux for 17 hours
  4. extractionextracted with water, saturated aqueous sodium bicarbonate, water
  5. dry with materialdried with brine and over sodium sulfate
  6. customAn attempt was purify the crude material by Biotage® chromatography
  7. customfor 16 hours
  8. customevaporated
  9. customthe residue purified by mass-directed autopreparative HPLC

Sources & evidence

ORD record
ord-226bde8a3698467aba4d78807100d28f
Source dataset
uspto-grants-2006_08
Patent number
US07091237B2

Linked notes

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