Triethylamine → 2-{4-[5-(3-Fluoro-phenyl)-pent-4-ynyloxyl]-2-methyl-phenoxy}-2-methyl-propionic acid

HRID 852392Notes

Reaction equation

HRID 852392 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4](I)[CH:3]=1.[CH3:9][C:10]([O:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][CH2:25][C:26]#[CH:27])=[CH:18][C:17]=1[CH3:28])([CH3:14])[C:11]([OH:13])=[O:12].C(N(CC)CC)C>C(#N)C.[Cu]I>[F:1][C:2]1[CH:3]=[C:4]([C:27]#[C:26][CH2:25][CH2:24][CH2:23][O:22][C:19]2[CH:20]=[CH:21][C:16]([O:15][C:10]([CH3:14])([CH3:9])[C:11]([OH:13])=[O:12])=[C:17]([CH3:28])[CH:18]=2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 707251-Fluoro-3-iodobenzeneHCID 866025422-Methyl-2-(2-methyl-4-pent-4-ynyloxy-phenoxy)-propionic acid

Product 1

HCID 116678292-{4-[5-(3-Fluoro-phenyl)-pent-4-ynyloxyl]-2-methyl-phenoxy}-2-methyl-propionic acidYield 67.5%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6342AcetonitrileSolvent

Procedure

A degassed (argon) solution of 0.098 g (0.44 mmol) 1-fluoro-3-iodobenzene in 4 ml acetonitrile was treated with 0.111 g (0.40 mmol) 2-methyl-2-(2-methyl-4-pent-4-ynyloxy-phenoxy)-propionic acid (example 26B]), 0.014 g (0.02 mmol) PdCl2(Ph3P)2, 0.004 g (0.02 mmol) of CuI and 0.17 ml (1.20 mmol) triethylamine. The reaction was stirred for 2.5 h and then extracted with chilled aqueous 10% KHSO4/ether (three times). The organic phases were washed with aqueous 10% NaCl, dried (Na2SO4) and evaporated. Purification was done by flash-chromatography on silica gel (1. n-heptane/EtOAc 4:1 and 2. CH2Cl2/MeOH 2%-10%). The pure fractions were evaporated, dissolved in ether and washed with aqueous 10% KHSO4/ether (three times). The organic phase was dried (Na2SO4) and evaporated to yield 0.10 g of the title compound as an orange viscous oil.

Workup

  1. extractionextracted with chilled aqueous 10% KHSO4/ether (three times)
  2. washThe organic phases were washed with aqueous 10% NaCl
  3. dry with materialdried (Na2SO4)
  4. customevaporated
  5. customPurification
  6. customThe pure fractions were evaporated
  7. dissolutiondissolved in ether
  8. washwashed with aqueous 10% KHSO4/ether (three times)
  9. dry with materialThe organic phase was dried (Na2SO4)
  10. customevaporated

Sources & evidence

ORD record
ord-f8e2510ef1064bb69c498adac866f4db
Source dataset
uspto-grants-2007_08
Patent number
US07253192B2

Reaction notes

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