Thionyl Chloride → Pentyl 2-[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]propionate

HRID 433692Notes

Reaction equation

HRID 433692 reaction equation
[Cl:1][C:2]1[CH:20]=[C:19]([F:21])[C:18]([N:22]2[C:27](=[O:28])[CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[N:24]([CH3:33])[C:23]2=[O:34])=[CH:17][C:3]=1[O:4][C:5]1[CH:16]=[CH:15][CH:14]=[CH:13][C:6]=1[O:7][CH:8]([CH3:12])[C:9]([OH:11])=[O:10].S(Cl)(Cl)=O>O1CCCC1>[Cl:1][C:2]1[CH:20]=[C:19]([F:21])[C:18]([N:22]2[C:27](=[O:28])[CH:26]=[C:25]([C:29]([F:30])([F:31])[F:32])[N:24]([CH3:33])[C:23]2=[O:34])=[CH:17][C:3]=1[O:4][C:5]1[CH:16]=[CH:15][CH:14]=[CH:13][C:6]=1[O:7][CH:8]([CH3:12])[C:9]([O:11][CH2:17][CH2:3][CH2:2][CH2:20][CH3:19])=[O:10]

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 219335762-[2-{2-Chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]propionic acid

Product 1

HCID 21933572Pentyl 2-[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]propionate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]propionic acid is dissolved in tetrahydrofuran, to this is added thionyl chloride while stirring, then, the mixture is heated while stirring under reflux condition. Then, the solution is allowed to cool, concentrated, then, dissolved in tetrahydrofuran (hereinafter, referred to as Solution A). Tetrahydrofuran is added to 1-pentyl alcohol, and Solution A is added to this, then, pyridine is added. The mixture is stirred at room temperature, then, 2% aqueous hydrochloric acid is poured into the reaction solution, and extracted with ethyl acetate. The organic layer is washed with saturated saline, and dried over magnesium sulfate, then, concentrated. The residue is subjected to silica gel column chromatography (eluent: hexane/ethyl acetate=5/1) to obtain pentyl 2-[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]propionate [compound 3-189 of the present invention].

Workup

  1. temperaturethe mixture is heated
  2. stirringwhile stirring
  3. temperatureunder reflux condition
  4. temperatureto cool
  5. concentrationconcentrated
  6. dissolutiondissolved in tetrahydrofuran (hereinafter,
  7. additionTetrahydrofuran is added to 1-pentyl alcohol, and Solution A
  8. additionis added to this, then, pyridine
  9. additionis added
  10. stirringThe mixture is stirred at room temperature
  11. addition2% aqueous hydrochloric acid is poured into the reaction solution
  12. extractionextracted with ethyl acetate
  13. washThe organic layer is washed with saturated saline
  14. dry with materialdried over magnesium sulfate
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-6029e1121e984f12b8c49f46b025b01a
Source dataset
uspto-grants-2003_12
Patent number
US06667413B2

Reaction notes

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