Dimethyl Sulfate → HCID 178423319, compound

HRID 1371122Notes

Reaction equation

HRID 1371122 reaction equation
Cl.[CH3:2][CH:3]1[CH2:8][CH:7]([C:9]2[NH:14][C:13]3=[CH:15][CH:16]=[N:17][C:12]3=[CH:11][N:10]=2)[CH2:6][CH:5]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[NH:4]1.[CH2:24]([Li])CCC.S(OC)(OC)(=O)=O>C1COCC1>[CH3:2][CH:3]1[CH2:8][CH:7]([C:9]2[NH:14][C:13]3=[CH:15][CH:16]=[N:17][C:12]3=[CH:11][N:10]=2)[CH:6]([CH3:24])[CH:5]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[NH:4]1

Participants

5

Reactant 3

HCID 6497Dimethyl SulfateHCID 178418339ButyllithiumHCID 178423311HCID 178423311, compound

Product 1

HCID 178423319HCID 178423319, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A suspension of 2-methyl-6-phenyl-4-piperidylpyrrolo[3,2-d]pyridine (Example 35) (57 mg, 0.20 mmol) in THF (3 mL) was placed under a N2 atmosphere and cooled with a dry-ice bath to −78° C. n-Butyl lithium (Aldrich Chemical Company) (360 μL, 0.90 mmol, 4.5 equiv of a 2.5 M solution in hexanes) was added slowly. The reaction mixture was stirred at −78° C. for 1 h and allowed to warmed to 0° C. Dimethyl sulfate (Eastman Kodak Company) (73.8 mg, 0.60 mmol, 3.0) was added slowly at 0° C. The solution was allowed to warm to room temperature and stir overnight. The reaction was quenched by the addition of 10% NH4Cl (3 mL) and the THF was evaporated under reduced pressure. The solution was extracted with CHCl3 (3×50 mL), and the combined organic layers were washed with saturated NaCl, dried over Na2SO4, filtered and concentrated with a rotary evaporator. The crude material was purified by flash chromatography on silica gel with a gradient eluant of EtOAc(0-20%):hexanes (100-80%) to provide 20 mg (34%) of the title compound as a white solid [30 mg (53%) of recovered starting material was also obtained]. Mp: 131-132° C. 1H NMR (acetone-d6, 400 MHz): δ 7.68 (d, 2, J=7.0), 7.54 (t, 2, J=7.0), 7.47 (t, 1, J=7.0), 3.84 (s, 3), 3.40 (t, 4, J=4.9), 2.50 (s, 3), 1.78 (m, 4), 1.70 (m, 2). MS m/z: 307 (M+1).

Workup

  1. additionwas added slowly
  2. temperatureallowed to warmed to 0° C
  3. temperatureto warm to room temperature
  4. stirringstir overnight
  5. customThe reaction was quenched by the addition of 10% NH4Cl (3 mL)
  6. customthe THF was evaporated under reduced pressure
  7. extractionThe solution was extracted with CHCl3 (3×50 mL)
  8. washthe combined organic layers were washed with saturated NaCl
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated with a rotary evaporator
  12. customThe crude material was purified by flash chromatography on silica gel with a gradient eluant of EtOAc(0-20%)

Sources & evidence

ORD record
ord-d94768f1fc55460d833c7a8e95b30277
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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