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

HRID 1762257Notes

Reaction equation

HRID 1762257 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([F:9])[C:5](F)=[N:6][CH:7]=1.[OH:10][C:11]1[CH:23]=[CH:22][C:14]([O:15][CH:16]([CH3:21])[C:17]([O:19][CH3:20])=[O:18])=[CH:13][CH:12]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.C1OCCOCCOCCOCCOCCOC1>[Cl:1][C:2]1[CH:3]=[C:4]([F:9])[C:5]([O:10][C:11]2[CH:12]=[CH:13][C:14]([O:15][CH:16]([CH3:21])[C:17]([O:19][CH3:20])=[O:18])=[CH:22][CH:23]=2)=[N:6][CH:7]=1

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 63%

Reagents, catalysts & solvents 2

HCID 2855718-Crown-6CatalystHCID 6342AcetonitrileSolvent2×

Procedure

A solution of 14.95 g (0.10 mol) of 5-chloro-2,3-difluoropyridine in 30 ml of acetonitrile is added dropwise to a mixture of 21.6 g (0.11 mol) of methyl 2-(4-hydroxyphenoxy)propionate, 15.2 g (0.11 mol) of potassium carbonate, 1.45 g (0.0055 mol) of 18-crown-6 and 100 ml of acetonitrile and the reaction mixture is then heated for 40 hours to a temperature in the range from 50° to 60° C. The mixture is taken up in ice water, the organic phase is separated, the aqueous phase is extracted three times with ethyl acetate and the combined organic phases are dried and concentrated by evaporation, affording an oily residue which for purification is dissolved in a mixture of hexane and ethyl acetate and filtered through silica gel. The solvent is evaporated off, affording from the filtrate 20.4 g (63% of theory) of methyl 2-[4-(5-chloro-3-fluoropyridin-2-yloxy)phenoxy]propionate, m.p. 58° -59° C.

Workup

  1. temperaturethe reaction mixture is then heated for 40 hours to a temperature in the range from 50° to 60° C
  2. customthe organic phase is separated
  3. extractionthe aqueous phase is extracted three times with ethyl acetate
  4. customthe combined organic phases are dried
  5. concentrationconcentrated by evaporation
  6. customaffording an oily residue which
  7. customfor purification
  8. dissolutionis dissolved in a mixture of hexane and ethyl acetate
  9. filtrationfiltered through silica gel
  10. customThe solvent is evaporated off

Sources & evidence

ORD record
ord-ebc39beeb6354e9aa5057b755ce13684
Source dataset
uspto-grants-1989_05
Patent number
US04831148

Reaction notes

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