Methyl 4-pentynoate → 5-{2-(2-methoxycarbonylethyl)-3-[6-(4-methoxyphenyl)-(5E)-5-hexenyloxy]-6-pyridyl}-4-pentynoic acid methyl ester

HRID 55265Notes

Reaction equation

HRID 55265 reaction equation
[CH3:1][O:2][C:3](=[O:28])[CH2:4][CH2:5][C:6]1[C:11]([O:12][CH2:13][CH2:14][CH2:15][CH2:16]/[CH:17]=[CH:18]/[C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)=[CH:10][CH:9]=[C:8](I)[N:7]=1.[CH3:29][O:30][C:31](=[O:36])[CH2:32][CH2:33][C:34]#[CH:35]>C(N(CC)CC)C.[Cu]I>[CH3:29][O:30][C:31](=[O:36])[CH2:32][CH2:33][C:34]#[C:35][C:8]1[N:7]=[C:6]([CH2:5][CH2:4][C:3]([O:2][CH3:1])=[O:28])[C:11]([O:12][CH2:13][CH2:14][CH2:15][CH2:16]/[CH:17]=[CH:18]/[C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)=[CH:10][CH:9]=1

Participants

5

Reactant 2

HCID 543061Methyl 4-pentynoateHCID 867507633-{6-iodo-3-[6-(4-methoxyphenyl)-(5E)-5-hexenyloxy]-2-pyridyl}-propionic acid methyl ester

Product 1

HCID 677037425-{2-(2-methoxycarbonylethyl)-3-[6-(4-methoxyphenyl)-(5E)-5-hexenyloxy]-6-pyridyl}-4-pentynoic acid methyl esterYield 96.4%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8471TriethylamineSolvent

Procedure

11 mg of bis-triphenylphosphine-palladium(II) chloride and 1.5 mg of copper(I) iodide are added to a solution of 300 mg of 3-{6-iodo-3-[6-(4-methoxyphenyl)-(5E)-5-hexenyloxy]-2-pyridyl}-propionic acid methyl ester and 68 mg of 4-pentynoic acid methyl ester in 5 ml of triethylamine, and the mixture is stirred for 20 hours at room temperature. The reaction mixture is filtered, the filter residue is washed with ethyl acetate and the filtrate is concentrated by evaporation. The residue is taken up in water, shaken out with ethyl acetate, dried on sodium sulfate and concentrated by evaporation. The crude product is chromatographed on silica gel with hexane/0-10% ethyl acetate and for complete purification subjected to high-pressure liquid chromatography on reversed-phase silica gel (Nova-Pak HR C18) with acetonitrile/water=75/25. 280 mg of 5-{2-(2-methoxycarbonylethyl)-3-[6-(4-methoxyphenyl)-(5E)-5-hexenyloxy]-6-pyridyl}-4-pentynoic acid methyl ester is obtained as colorless oil.

Workup

  1. filtrationThe reaction mixture is filtered
  2. washthe filter residue is washed with ethyl acetate
  3. concentrationthe filtrate is concentrated by evaporation
  4. stirringshaken out with ethyl acetate
  5. customdried on sodium sulfate
  6. concentrationconcentrated by evaporation
  7. customThe crude product is chromatographed on silica gel with hexane/0-10% ethyl acetate and for complete purification

Sources & evidence

ORD record
ord-91ffc74730f84d33aea7075ee07a5a2f
Source dataset
uspto-grants-1997_04
Patent number
US05624943

Reaction notes

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