Triethylamine → 2-Methyl-2-{2-methyl-4-[5-(5-trifluoromethyl-pyridin-2-yl)-pent-4-ynyloxy]-phenoxy}-propionic acid ethyl ester

HRID 852381Notes

Reaction equation

HRID 852381 reaction equation
[CH2:1]([O:3][C:4](=[O:22])[C:5]([CH3:21])([O:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][C:18]#[CH:19])=[CH:10][C:9]=1[CH3:20])[CH3:6])[CH3:2].Br[C:24]1[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][N:25]=1.CCN(CC)CC>C(#N)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[CH2:1]([O:3][C:4](=[O:22])[C:5]([CH3:21])([O:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][C:18]#[C:19][C:24]2[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][N:25]=2)=[CH:10][C:9]=1[CH3:20])[CH3:6])[CH3:2]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 27364342-Bromo-5-(trifluoromethyl)pyridineHCID 866025402-Methyl-2-(2-methyl-4-pent-4-ynyloxy-phenoxy)-propionic acid ethyl ester

Product 1

HCID 694591772-Methyl-2-{2-methyl-4-[5-(5-trifluoromethyl-pyridin-2-yl)-pent-4-ynyloxy]-phenoxy}-propionic acid ethyl esterYield 75.6%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolvent

Procedure

A degassed (argon) solution of 152 mg (0.50 mmol) 2-methyl-2-(2-methyl-4-pent-4-ynyloxy-phenoxy)-propionic acid ethyl ester (example 13A]), 124 mg (0.55 mmol) 2-bromo-5-(trifluoromethyl)pyridine and 0.21 ml (1.5 mmol) Et3N in 5 ml acetonitrile was treated with 18 mg (0.03 mmol) of PdCl2(PPh3)2 and 3 mg (0.03 mmol) of CuI. After stirring for 3 h at room temperature the reaction mixture was partitioned between cold aqueous 10% KHSO4 and ether (three times). Washing of the organic layer with aqueous 10% NaCl solution, drying (Na2SO4) and evaporation of the solvents, followed by flash chromatography (SiO2, n-heptane/EtOAc 95:5 to 9:1) yielded 170 mg of the title compound as yellow viscous oil.

Workup

  1. customwas partitioned between cold aqueous 10% KHSO4 and ether (three times)
  2. washWashing of the organic layer with aqueous 10% NaCl solution
  3. customdrying
  4. custom(Na2SO4) and evaporation of the solvents

Sources & evidence

ORD record
ord-ebf88735b72e455eb4745fd699a49dce
Source dataset
uspto-grants-2007_08
Patent number
US07253192B2

Reaction notes

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