4-Chloro-2-(methylthio)pyrimidine-5-carboxylic acid ethyl ester → HCID 71224526, compound

HRID 2172380Notes

Reaction equation

HRID 2172380 reaction equation
C([N-]C(C)C)(C)C.[Li+].[C:9]1([CH:15]([O:18][Si](C)(C)C)[C:16]#[N:17])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.Cl[C:24]1[C:29]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=CN=[C:26]([S:35][CH3:36])[N:25]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[C:15]([C:16]1[C:29]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[CH:24][N:25]=[C:26]([S:35][CH3:36])[N:17]=1)(=[O:18])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

6

Reactant 4

HCID 800084-Chloro-2-(methylthio)pyrimidine-5-carboxylic acid ethyl esterHCID 6054842-Phenyl-2-((trimethylsilyl)oxy)acetonitrileHCID 2724141Tetrabutylammonium FluorideHCID 2724682Lithium diisopropylamide

Product 1

HCID 71224526HCID 71224526, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a cold (−78° C.) freshly-prepared solution of lithium diisopropylamide (2.62 mmol) in THF (5 mL) was added a solution of 2-phenyl-2-(trimethylsilyloxy)acetonitrile (0.5 ml, 2.382 mmol) in THF (4 mL). The solution was stirred for 2 hours, and a solution of ethyl 4-chloro-2-(methylthio)pyrimidine-5-carboxylate (554 mg, 2.382 mmol) in THF (3 mL) was added dropwise. The cold bath was removed, and the reaction warmed to room temperature. The reaction mixture was quenched by the addition of saturated sodium bicarbonate solution (15 mL) and ethyl acetate (15 mL). The layers were separated, and the aqueous extracted with addition ethyl acetate. The combined organics were dried with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was dissolved in THF (15 mL), and a solution of tetrabutyl ammonium fluoride (3.0 mmol, 3.0 mL, 1 M in THF) was added. The reaction mixture was stirred for 1 hour, and quenched by the addition of saturated sodium bicarbonate solution (15 mL) and ethyl acetate (15 mL). The layers were separated, and the aqueous layer extracted with addition ethyl acetate. The combined organics were dried with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel, eluting with a gradient of hexane to 30% ethyl acetate in hexane, to give the title compound. MS ESI(+) m/z 302.9 [M+H]+.

Workup

  1. customThe cold bath was removed
  2. customThe reaction mixture was quenched by the addition of saturated sodium bicarbonate solution (15 mL) and ethyl acetate (15 mL)
  3. customThe layers were separated
  4. extractionthe aqueous extracted with addition ethyl acetate
  5. dry with materialThe combined organics were dried with anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. dissolutionThe residue was dissolved in THF (15 mL)
  9. stirringThe reaction mixture was stirred for 1 hour
  10. customquenched by the addition of saturated sodium bicarbonate solution (15 mL) and ethyl acetate (15 mL)
  11. customThe layers were separated
  12. extractionthe aqueous layer extracted with addition ethyl acetate
  13. dry with materialThe combined organics were dried with anhydrous sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure
  16. customThe residue was purified by chromatography on silica gel
  17. washeluting with a gradient of hexane to 30% ethyl acetate in hexane

Sources & evidence

ORD record
ord-3aa462dec4b840429b0192acbdbf9ff1
Source dataset
uspto-grants-2015_06
Patent number
US09051327B2

Reaction notes

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