Hydrochloric Acid → 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

HRID 1280339Notes

Reaction equation

HRID 1280339 reaction equation
[Cl:1][C:2]1[CH:21]=[C:20]([F:22])[C:19]([N:23]2[C:28](=[O:29])[CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[N:25]([CH3:34])[C:24]2=[O:35])=[CH:18][C:3]=1[O:4][C:5]1[CH:17]=[CH:16][CH:15]=[CH:14][C:6]=1[O:7][CH:8]([CH3:13])[C:9]([O:11]C)=[O:10].Cl.O.C(OCC)(=O)C>O1CCOCC1>[Cl:1][C:2]1[CH:21]=[C:20]([F:22])[C:19]([N:23]2[C:28](=[O:29])[CH:27]=[C:26]([C:30]([F:31])([F:32])[F:33])[N:25]([CH3:34])[C:24]2=[O:35])=[CH:18][C:3]=1[O:4][C:5]1[CH:17]=[CH:16][CH:15]=[CH:14][C:6]=1[O:7][CH:8]([CH3:13])[C:9]([OH:11])=[O:10]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 8857Ethyl AcetateHCID 12115508Methyl 2-[2-(2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]propionate

Product 1

HCID 219335762-[2-{2-Chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]propionic acidYield 51.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

0.365 g of methyl 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 3-1 of the present invention) was dissolved in 4 ml of 1,4-dioxane, to this was added a mixed solution of 1 ml of conc. hydrochloric acid and 1 ml of water while stirring, then, the mixture was heated for 5 hours and 45 minutes while stirring under reflux condition. Thereafter, the solution was allowed to cool, and ice water was poured into the reaction solution, ethyl acetate and saturated saline were added to the solution which was separated subsequently, and aqueous sodium hydrogen carbonate was added to the organic layer before separation, aqueous hydrochloric acid was added to the aqueous layer to acidify it, then, ethyl acetate was added before separation, the organic layer was washed with saturated saline, and dried over magnesium sulfate, then, concentrated to obtain 0.183 g of 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.

Workup

  1. temperaturethe mixture was heated for 5 hours and 45 minutes
  2. stirringwhile stirring
  3. temperatureunder reflux condition
  4. temperatureto cool
  5. additionwere added to the solution which
  6. customwas separated subsequently
  7. additionaqueous sodium hydrogen carbonate was added to the organic layer before separation, aqueous hydrochloric acid
  8. additionwas added to the aqueous layer
  9. additionethyl acetate was added before separation
  10. washthe organic layer was washed with saturated saline
  11. dry with materialdried over magnesium sulfate
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-8f6c813730fa45fab280ca2c0bdd512b
Source dataset
uspto-grants-2002_09
Patent number
US06451740B2

Reaction notes

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