Potassium Carbonate → Methyl 2-[4-(5-chloro-3-fluoropyridin-2-yloxy)phenoxy]propionate

HRID 359645Notes

Reaction equation

HRID 359645 reaction equation
[CH3:1][O:2][C:3](=[O:14])[CH:4]([O:6][C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1)[CH3:5].C(=O)([O-])[O-].[K+].[K+].[Cl:21][C:22]1[CH:23]=[C:24]([F:29])[C:25](F)=[N:26][CH:27]=1>C(#N)C.C1OCCOCCOCCOCCOCCOC1>[CH3:1][O:2][C:3](=[O:14])[CH:4]([O:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][C:25]2[C:24]([F:29])=[CH:23][C:22]([Cl:21])=[CH:27][N:26]=2)=[CH:9][CH:8]=1)[CH3:5]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 366926Propanoic acid, 2-(4-hydroxyphenoxy)-, methyl esterHCID 27832485-Chloro-2,3-difluoropyridine

Product 1

HCID 15592836Methyl 2-[4-(5-chloro-3-fluoropyridin-2-yloxy)phenoxy]propionateYield 62.6%

Reagents, catalysts & solvents 2

HCID 2855718-Crown-6CatalystHCID 6342AcetonitrileSolvent2×

Procedure

To a stirred mixture of 21.6 g (0.11 mol) of 2-(4-hydroxyphenoxy)-propionic acid methyl ester, 15.2 g (0.11 mol) of potassium carbonate, 1.45 g (0.0055 mol) of 18-Crown-6 ether and 100 ml of acetonitrile is added dropwise a solution of 14.95 g (0.10 mol) of 5-chloro-2,3-difluoropyridine in 30 ml of acetonitrile and the mixture is heated at a temperature of 50° to 60° C. during 40 hours. The mixture is then poured into ice/water. The organic material is extracted with ethyl acetate, washed with a saturated salt solution, dried over magnesium sulfate, filtered and evaporated. The oily residue is purified by chromatography over a silica gel column with a hexane/ethyl acetate 3:1 solvent. After evaporation of the solvent one obtain 20.4 g of the above ester (63% of the theory) is obtained in crystalline form. The melting point is 63°-64° C.

Workup

  1. temperaturethe mixture is heated at a temperature of 50° to 60° C. during 40 hours
  2. extractionThe organic material is extracted with ethyl acetate
  3. washwashed with a saturated salt solution
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe oily residue is purified by chromatography over a silica gel column with a hexane/ethyl acetate 3:1 solvent
  8. customAfter evaporation of the solvent one

Sources & evidence

ORD record
ord-797f56278f6a4c2b893d8a429875c6f1
Source dataset
uspto-grants-1991_03
Patent number
US05002604

Reaction notes

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