Acetic Acid → Methyl [2-{2-chloro-4-fluoro-5-[2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate

HRID 493944Notes

Reaction equation

HRID 493944 reaction equation
O[C:2](O)([C:28]([F:31])([F:30])[F:29])[CH2:3][C:4]([NH:6][C:7]1[C:8]([F:27])=[CH:9][C:10]([Cl:26])=[C:11]([CH:25]=1)[O:12][C:13]1[CH:24]=[CH:23][CH:22]=[CH:21][C:14]=1[O:15][CH2:16][C:17]([O:19][CH3:20])=[O:18])=[O:5].O1CCCC1.C(O)(=O)C.[O-:42][C:43]#[N:44].[K+]>O>[Cl:26][C:10]1[CH:9]=[C:8]([F:27])[C:7]([N:6]2[C:4](=[O:5])[CH:3]=[C:2]([C:28]([F:31])([F:30])[F:29])[NH:44][C:43]2=[O:42])=[CH:25][C:11]=1[O:12][C:13]1[CH:24]=[CH:23][CH:22]=[CH:21][C:14]=1[O:15][CH2:16][C:17]([O:19][CH3:20])=[O:18]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8028TetrahydrofuranHCID 11378442Potassium cyanateHCID 21947104Methyl[2-(5-{3,3-dihydroxy-4,4,4-trifluorobutyryl}amino-2-chloro-4-fluorophenoxy)phenoxy]acetate

Product 1

HCID 12115501Methyl [2-{2-chloro-4-fluoro-5-[2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetateYield 66%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of 1.0 g of crude methyl [2 -(5-{3,3-dihydroxy-4,4,4-trifluorobutyryl}amino-2-chloro-4-fluorophenoxy)phenoxy]acetate and 3 ml of tetrahydrofuran were added 4 ml of acetic acid and 0.87 g of potassium cyanate, and the mixture was stirred at room temperature for 6 hours and then heated at reflux at 120° C. for 2 hours. After cooling, 30 ml of water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate solution, water and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give 0.67 g of methyl [2-{2-chloro-5-[2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]-4-fluorophenoxy}phenoxy]acetate.

Workup

  1. temperatureheated
  2. temperatureat reflux at 120° C. for 2 hours
  3. temperatureAfter cooling
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe organic layer was washed with saturated aqueous sodium bicarbonate solution, water and saturated aqueous sodium chloride solution
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-665f7a6406c84767be6b125220ca4365
Source dataset
uspto-grants-2009_05
Patent number
US07538072B2

Reaction notes

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