Dimethyl Sulfate → 2,4(1H,3H)-Pyrimidinedione, 3-(4-chloro-2-fluoro-5-(1-methylethoxy)phenyl)-1,6-dimethyl-

HRID 1722942Notes

Reaction equation

HRID 1722942 reaction equation
[Cl:1][C:2]1[C:7]([O:8][CH:9]([CH3:11])[CH3:10])=[CH:6][C:5]([NH:12][C:13](=[O:23])[NH:14]/[C:15](/[CH3:22])=[CH:16]\[C:17]([O:19]CC)=O)=[C:4]([F:24])[CH:3]=1.[H-].[Na+].S(OC)(O[CH3:31])(=O)=O>CN(C)C=O.C(O)(C)C.CN(C)C=O>[Cl:1][C:2]1[C:7]([O:8][CH:9]([CH3:10])[CH3:11])=[CH:6][C:5]([N:12]2[C:17](=[O:19])[CH:16]=[C:15]([CH3:22])[N:14]([CH3:31])[C:13]2=[O:23])=[C:4]([F:24])[CH:3]=1

Participants

6

Reactant 3

HCID 6497Dimethyl SulfateHCID 24758Sodium hydrideHCID 70395142HCID 70395142, compound

Product 1

HCID 1354002,4(1H,3H)-Pyrimidinedione, 3-(4-chloro-2-fluoro-5-(1-methylethoxy)phenyl)-1,6-dimethyl-

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 20197112Isopropanol dimethylformamideSolvent

Procedure

A solution of 9.00 g of ethyl 3-[3-(4-chloro-2-fluoro-5-isopropoxyphenyl)ureido]-crotonate in 100 ml of anhydrous dimethylformamide is added dropwise at room temperature while stirring to a solution of 1.10 g of a 55% sodium hydride dispersion in 100 ml of isopropanol/dimethylformamide (1:1) and stirred for 1 hour. The reaction mixture is subsequently treated with 4.70 g of dimethYl sulphate and stirred at room temperature for 2 hours. The solvent is largely distilled off under reduced pressure and the residue is poured into 500 ml of water and extracted twice with 200 ml of ethyl acetate each time. The organic phases are washed with water, dried over anhydrous sodium sulphate and evaporated to dryness under reduced pressure. The residue is recrystallized from diethyl ether/n-hexane. There is obtained 3-(4-chloro-2-fluoro-5-isopropoxyphenyl)-1,6 -dimethyl-2,4(1H,3H)-pyrimidinedione, m.p. 149°-151° C.

Workup

  1. stirringstirred at room temperature for 2 hours
  2. distillationThe solvent is largely distilled off under reduced pressure
  3. additionthe residue is poured into 500 ml of water
  4. extractionextracted twice with 200 ml of ethyl acetate each time
  5. washThe organic phases are washed with water
  6. dry with materialdried over anhydrous sodium sulphate
  7. customevaporated to dryness under reduced pressure
  8. customThe residue is recrystallized from diethyl ether/n-hexane

Sources & evidence

ORD record
ord-db7a21edb72740e2bfdd87acee9c9830
Source dataset
uspto-grants-1989_08
Patent number
US04859229

Reaction notes

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