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

HRID 2278549Notes

Reaction equation

HRID 2278549 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, then insoluble material is filtered off, washing is carried out 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, extraction is carried out with 3 times approximately 350 ml of ethyl acetate, the combined organic extracts are washed with 500 ml of saturated NaCl solution, drying is carried out over MgSO4, filtration is carried out through a VF filter, and the resulting product is concentrated under vacuum. The compound obtained is purified by chromatography on silica gel (40-63 μm), elution being carried out with a mixture of EtOAc/n-heptane (2/8 v/v). 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. filtrationinsoluble material is filtered off
  3. washwashing
  4. concentrationthe filtrate is concentrated until a pasty residue
  5. customis obtained
  6. stirringAfter stirring
  7. extractionextraction
  8. washthe combined organic extracts are washed with 500 ml of saturated NaCl solution
  9. customdrying
  10. filtrationis carried out over MgSO4, filtration
  11. filtrationfilter
  12. concentrationthe resulting product is concentrated 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 EtOAc/n-heptane (2/8 v/v)
  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-c0349e6f18544b8aae2a6d0f0ad2f5d3
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

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