Potassium Iodide → Ethyl 2-(6-chloro-4-oxo-1,4-dihydropyrimidin-2-yl)acetate

HRID 2278539Notes

Reaction equation

HRID 2278539 reaction equation
[CH2:1]([O:3][C:4](=[O:15])[CH2:5][C:6]1[N:11]=[C:10]([Cl:12])[CH:9]=[C:8]([O:13]C)[N:7]=1)[CH3:2].C(#N)C.[I-].[K+].C[Si](C)(C)Cl>O>[CH2:1]([O:3][C:4](=[O:15])[CH2:5][C:6]1[NH:7][C:8](=[O:13])[CH:9]=[C:10]([Cl:12])[N:11]=1)[CH3:2]

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 6342AcetonitrileHCID 6397ChlorotrimethylsilaneHCID 86699270Ethyl 2-(4-chloro-6-methoxypyrimidin-2-yl)acetate

Product 1

HCID 136378677Ethyl 2-(6-chloro-4-oxo-1,4-dihydropyrimidin-2-yl)acetateYield 81%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

33 g of (4-chloro-6-methoxypyrimidin-2-yl)acetic acid ethyl ester (example 8b, step 2b) and 750 ml of acetonitrile are placed in a 1000 ml autoclave and then 71.2 g of potassium iodide and 55.85 ml of trimethylchlorosilane are added; an orangey-colored heterogeneous solution is obtained, which is stirred while heating under an argon pressure of 10 bar at 100° C. for 2 hours. The reaction medium is drawn off and then the insoluble material is filtered off and washed with 3 times approximately 100 ml of EtOAc, and the filtrate is concentrated until a pasty residue is obtained, which is taken up in 500 ml of water. After stirring and extraction with 3 times approximately 350 ml of ethyl acetate, the combined organic extracts are washed with 500 ml of saturated NaCl solution, dried over MgSO4, filtered through a VF filter, and concentrated under vacuum. The compound obtained is purified by chromatography on silica gel (40-63 μm), elution being carried out with a mixture of 2/8 v/v EtOAc/n-heptane. The fractions containing the expected compound are combined and evaporated. A solid is isolated, which is triturated from diisopropyl ether, filtered through sintered glass and dried. (4-Chloro-6-oxo-1,6-dihydropyrimidin-2-yl)acetic acid ethyl ester is isolated in the form of a beige solid: 25.2 g; yield 81%

Workup

  1. customan orangey-colored heterogeneous solution is obtained
  2. filtrationthe insoluble material is filtered off
  3. washwashed with 3 times approximately 100 ml of EtOAc
  4. concentrationthe filtrate is concentrated until a pasty residue
  5. customis obtained
  6. stirringAfter stirring
  7. extractionextraction with 3 times approximately 350 ml of ethyl acetate
  8. washthe combined organic extracts are washed with 500 ml of saturated NaCl solution
  9. dry with materialdried over MgSO4
  10. filtrationfiltered through a VF
  11. filtrationfilter
  12. concentrationconcentrated under vacuum
  13. customThe compound obtained
  14. customis purified by chromatography on silica gel (40-63 μm), elution
  15. additionbeing carried out with a mixture of 2/8 v/v EtOAc/n-heptane
  16. additionThe fractions containing the expected compound
  17. customevaporated
  18. customA solid is isolated
  19. customwhich is triturated from diisopropyl ether
  20. filtrationfiltered through sintered glass
  21. customdried

Sources & evidence

ORD record
ord-d1186a4f9bf044a6b1ce9fd7a73155e1
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

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