Acetic Acid → 3-{2-Chloro-4-fluoro-5-[2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-(methoxycarbonyl)methoxypyridine

HRID 1862229Notes

Reaction equation

HRID 1862229 reaction equation
[Cl:1][C:2]1[C:7]([O:8][C:9]2[C:10]([O:15][CH2:16][C:17]([O:19][CH3:20])=[O:18])=[N:11][CH:12]=[CH:13][CH:14]=2)=[CH:6][C:5]([NH:21][C:22](=[O:30])[CH2:23][C:24]([C:26]([F:29])([F:28])[F:27])=O)=[C:4]([F:31])[CH:3]=1.C(O)(=O)C.[O-:36][C:37]#[N:38].[K+]>O>[Cl:1][C:2]1[CH:3]=[C:4]([F:31])[C:5]([N:21]2[C:22](=[O:30])[CH:23]=[C:24]([C:26]([F:29])([F:28])[F:27])[NH:38][C:37]2=[O:36])=[CH:6][C:7]=1[O:8][C:9]1[C:10]([O:15][CH2:16][C:17]([O:19][CH3:20])=[O:18])=[N:11][CH:12]=[CH:13][CH:14]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 11378442Potassium cyanateHCID 86593477N-[4-chloro-2-fluoro-5-{2-(methoxycarbonyl)methoxy-3-pyridyloxy}phenyl]tri fluoroacetoacetamide

Product 1

HCID 186192103-{2-Chloro-4-fluoro-5-[2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-(methoxycarbonyl)methoxypyridineYield 40.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of 0.71 g of N-[4-chloro-2-fluoro-5-{2-(methoxycarbonyl)methoxy-3-pyridyloxy}phenyl]trifluoroacetoacetamide and 2 ml of acetic acid, 0.33 g of potassium cyanate was added, and the mixture was stirred at 50° C. for 1 hour, then, at 110° C. for 1.5 hours. After cooling, water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate solution, and saturated saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 0.30 g of 3-{2-chloro-4-fluoro-5-[2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-(methoxycarbonyl)methoxypyridine.

Workup

  1. additionwas added
  2. waitat 110° C. for 1.5 hours
  3. temperatureAfter cooling
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe organic layer was washed with saturated aqueous sodium bicarbonate solution, and saturated saline
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f765555b42c04d43bcb0cd877b626fb8
Source dataset
uspto-grants-2003_03
Patent number
US06537948B1

Reaction notes

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