p-Toluenesulfonic acid → Methyl 2-[4-(5-chloro-3-fluoropyridin-2-yloxy)phenoxy]propionate

HRID 1285093Notes

Reaction equation

HRID 1285093 reaction equation
[OH-].[Na+].[OH:3][C:4]1[CH:15]=[CH:14][C:7]([O:8][CH:9]([CH3:13])[C:10]([OH:12])=[O:11])=[CH:6][CH:5]=1.[Cl:16][C:17]1[CH:18]=[C:19]([F:24])[C:20](F)=[N:21][CH:22]=1.[C:25]1(C)C=CC(S(O)(=O)=O)=CC=1.CC1CCCCC1>CS(C)=O.O>[F:24][C:19]1[C:20]([O:3][C:4]2[CH:5]=[CH:6][C:7]([O:8][CH:9]([CH3:13])[C:10]([O:12][CH3:25])=[O:11])=[CH:14][CH:15]=2)=[N:21][CH:22]=[C:17]([Cl:16])[CH:18]=1

Participants

8

Reactant 5

HCID 6101p-Toluenesulfonic acidHCID 7962MethylcyclohexaneHCID 14798Sodium HydroxideHCID 1011822-(4-Hydroxy-phenoxy)-propionic acidHCID 27832485-Chloro-2,3-difluoropyridine

Product 1

HCID 15592836Methyl 2-[4-(5-chloro-3-fluoropyridin-2-yloxy)phenoxy]propionateYield 654,960.375%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

A solution of NaOH (2.7 g, 0.068 mol) in a few ml of water was added to 2-(4-hydroxyphenoxy)propionic acid (6.09 g, 0.033 mol) in 55 ml DMSO and the mixture was stirred for 20 minutes under nitrogen. 5-Chloro-2,3-difluoropyridine (5.0 g, 0.033 mol) was added and the mixture was heated at 70° C. for 5 hours. The reaction was then poured over ice and extracted with CH2Cl2. The organic layer was washed with water, dried over Na2SO4 and the solvent removed by rotary evaporation. The residual oil was dissolved in 130 ml dry methanol, p-toluene sulfonic acid (0.5 g, 0.003 mmol) was added and the mixture was stirred at room temperature for 24 hours. The methanol was removed by rotary evaporation. The residue was taken up in ether, washed with dilute aqueous NaOH, and dried over Na2SO4. The ether was removed by rotary evaporation to yield a tan oil which solidified on trituration with methylcyclohexane to give a white solid (6.4 g, 59%, m.p. 53°-56° C.).

Workup

  1. additionThe reaction was then poured over ice
  2. extractionextracted with CH2Cl2
  3. washThe organic layer was washed with water
  4. dry with materialdried over Na2SO4
  5. customthe solvent removed by rotary evaporation
  6. dissolutionThe residual oil was dissolved in 130 ml dry methanol
  7. stirringthe mixture was stirred at room temperature for 24 hours
  8. customThe methanol was removed by rotary evaporation
  9. washwashed with dilute aqueous NaOH
  10. dry with materialdried over Na2SO4
  11. customThe ether was removed by rotary evaporation
  12. customto yield a tan oil which

Sources & evidence

ORD record
ord-2303107bc84e454db0ef72640cca5daf
Source dataset
uspto-grants-1986_01
Patent number
US04565568

Reaction notes

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