Tetrahydrofuran → HCID 21834454, compound

HRID 1740958Notes

Reaction equation

HRID 1740958 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([N:9]2[C:13]([CH3:14])=[CH:12][CH:11]=[C:10]2[CH3:15])[CH:3]=1.C([Li])CCC.O1CCCC1.Br[CH2:27][CH2:28][CH2:29][N:30]1[C:34]([CH3:35])=[CH:33][CH:32]=[C:31]1[CH3:36]>C(OCC)C.CCCCCC>[CH3:1][C:2]1[CH:7]=[C:6]([CH2:8][CH2:27][CH2:28][CH2:29][N:30]2[C:34]([CH3:35])=[CH:33][CH:32]=[C:31]2[CH3:36])[N:5]=[C:4]([N:9]2[C:13]([CH3:14])=[CH:12][CH:11]=[C:10]2[CH3:15])[CH:3]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 127942501-(3-bromopropyl)-2,5-dimethyl-1H-pyrroleHCID 224907362-(2,5-Dimethyl-1H-pyrrol-1-yl)-4,6-dimethylpyridineHCID 178418339Butyllithium

Product 1

HCID 21834454HCID 21834454, compoundYield 80.4%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-17.5 °C

Procedure

A solution of 297 mg (1.49 mmol) of 4,6-dimethyl-2-(2,5-dimethylpyrrol-1-yl)pyridine (from Example 53, Step A) in 1.5 mL of ethyl ether was added to a -20° C. solution prepared from 3.0 mL of ethyl ether and 1.2 mL (1.7 mmol) of 1.4 M n-butyllithium in hexane. The mixture was stirred for 1 h at -20 to -15° C. with the formation of a preciptate. Tetrahydrofuran (1.0 mL) was added, the resulting orange-red solution was cooled to .BECAUSE.45° C., and 400 mg (1.85 mmol) of 1-(3-bromopropyl)-2,5-dimethylpyrrole (S. P. Bruekelman, S. E. Leach, G. D. Meakins, and M. D. Tirel, J. Chem. Soc., Perkin Trans. 1, 1984, 2801-7) was added in one portion. The mixture was allowed to warm to 10° C. over 1.75 h, quenched with 10 mL of saturated aqueous ammonium chloride, and extracted with 20 mL of ethyl acetate. The organic layer was washed with 10 mL of saturated aqueous sodium chloride, dried (sodium sulfate), decanted, and evaporated. The residue was purified by flash column chromatography on 50 g of silica gel, eluting with 1.2 L of 5% ethyl acetate in hexane to give 402 mg (80% yield) of 4-methyl-2-(2,5-dimethylpyrrol-1-yl)-6-(4-(2,5-dimethylpyrrol-1-yl)butyl)pyridine as an almost colorless oil.

Workup

  1. temperaturethe resulting orange-red solution was cooled to .BECAUSE
  2. temperatureto warm to 10° C. over 1.75 h
  3. customquenched with 10 mL of saturated aqueous ammonium chloride
  4. extractionextracted with 20 mL of ethyl acetate
  5. washThe organic layer was washed with 10 mL of saturated aqueous sodium chloride
  6. dry with materialdried (sodium sulfate)
  7. customdecanted
  8. customevaporated
  9. customThe residue was purified by flash column chromatography on 50 g of silica gel
  10. washeluting with 1.2 L of 5% ethyl acetate in hexane

Sources & evidence

ORD record
ord-02d1d876400f41d2b3151789b14bdae7
Source dataset
uspto-grants-1999_10
Patent number
US05972975

Reaction notes

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