2-Methylpyridine → HCID 10429232, compound

HRID 1791337Notes

Reaction equation

HRID 1791337 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[Li]C(C)(C)C.[F:13][C:14]1[CH:15]=[CH:16][C:17]([O:36][CH3:37])=[C:18]([C:20]([CH3:35])([CH3:34])[CH2:21]/[C:22](=[N:27]/S(C(C)(C)C)=O)/[C:23]([F:26])([F:25])[F:24])[CH:19]=1>C1COCC1.CCCCC>[F:13][C:14]1[CH:15]=[CH:16][C:17]([O:36][CH3:37])=[C:18]([C:20]([CH3:34])([CH3:35])[CH2:21][C:22]([NH2:27])([CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=2)[C:23]([F:26])([F:25])[F:24])[CH:19]=1

Participants

6

Reactant 3

HCID 79752-MethylpyridineHCID 11326499HCID 11326499, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 10429232HCID 10429232, compoundYield 25.2%

Reagents, catalysts & solvents 2

HCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a chilled (−78 C.) solution of 0.05 mL (0.514 mmol) of 2-methylpyridine in 3 mL of dry THF was added 0.23 mL (0.4 mmol) of a 1.7 M solution of t-BuLi in pentane. The mixture turned a bright orange. After 10 min, a solution of 98 mg (0.257 mmol) of 2-methyl-propane-2-sulfinic acid [3-(5-fluoro-2-methoxy-phenyl)-3-methyl-1-trifluoromethyl-but-(Z)-ylidene]-amide in 0.5 mL of anhydrous THF was added. The reaction was then warmed to room temperature, quenched with aqueous ammonium chloride, stirred for 30 min and extracted with diethyl ether.(3×) The combined organic layers were dried (MgSO4), filtered and concentrated. The residue was dissolved in 2 mL of methanol, 3 drops of concentrated HCl were added and the reaction was warmed at 75° C. in a sealed tube. After 1 h, the reaction was cooled to room temperature, concentrated in vacuo, neutralized with aqueous sodium bicarbonate and extracted with EtOAc (3×). The combined organic layers were dried over (MgSO4), filtered and concentrated to afford an oil. The residue was purified by preparative thin layer chromatography eluting with hexanes-EtOAc (95:5) to afford 24 mg (25%) of the title compound.

Workup

  1. customquenched with aqueous ammonium chloride
  2. extractionextracted with diethyl ether
  3. dry with material(3×) The combined organic layers were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in 2 mL of methanol
  7. addition3 drops of concentrated HCl were added
  8. temperaturethe reaction was warmed at 75° C. in a sealed tube
  9. waitAfter 1 h
  10. temperaturethe reaction was cooled to room temperature
  11. concentrationconcentrated in vacuo
  12. extractionextracted with EtOAc (3×)
  13. dry with materialThe combined organic layers were dried over (MgSO4)
  14. filtrationfiltered
  15. concentrationconcentrated
  16. customto afford an oil
  17. customThe residue was purified by preparative thin layer chromatography
  18. washeluting with hexanes-EtOAc (95:5)

Sources & evidence

ORD record
ord-0f6a1e981b314c1c9c77fdfca8695d2a
Source dataset
uspto-grants-2006_07
Patent number
US07074806B2

Reaction notes

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