Trimethylaluminum → 5-(2-diethylamino-ethyl)-3-methyl-4-oxo-4,5,6,7,8,9-hexahydro-1H-1,5-diaza-cyclopentacyclooctene-2-carbaldehyde

HRID 2191499Notes

Reaction equation

HRID 2191499 reaction equation
C[Al](C)C.C(O[C:8]([C:10]1[C:11]([CH3:31])=[C:12]([C:24]([O:26]C(C)(C)C)=O)[NH:13][C:14]=1[CH2:15][CH2:16][CH2:17][CH2:18][N:19]([CH2:22][CH3:23])CC)=[O:9])C>C1(C)C=CC=CC=1>[CH2:12]([N:13]([CH2:14][CH3:10])[CH2:23][CH2:22][N:19]1[CH2:18][CH2:17][CH2:16][CH2:15][C:14]2[NH:13][C:12]([CH:24]=[O:26])=[C:11]([CH3:31])[C:10]=2[C:8]1=[O:9])[CH3:11]

Participants

4

Reactant 2

HCID 16682925Trimethylaluminum2×HCID 592500695-(4-diethylamino-butyl)-3-methyl-1H-pyrrole-2,4-dicarboxylic acid 2-tert-butyl ester 4-ethyl ester

Product 1

HCID 498404665-(2-diethylamino-ethyl)-3-methyl-4-oxo-4,5,6,7,8,9-hexahydro-1H-1,5-diaza-cyclopentacyclooctene-2-carbaldehydeYield 47.9%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

Trimethyl aluminum (489 μl, 2 mol/L) was dissolved in 3 ml of toluene under stirring, and added with the solution of 5-(4-diethylamino-butyl)-3-methyl-1H-pyrrole-2,4-dicarboxylic acid 2-tert-butyl ester 4-ethyl ester 60d (345 mg, 0.82 mmol) in 6 ml of toluene to the above solution at room temperature. Upon completion of the addition, the reaction mixture was stirred for 30 minutes at room temperature, heated to reflux for 2 hours in an oil bath, added with another trimethyl aluminum (900 μl, 2 mol/L) and refluxed for another 7 hours. After thin lay chromatography showed the disappearance of starting materials, the reaction mixture was quenched with water, added with hydrochloric acid solution (1 ml, 2 mol/L) and stirred for 30 minutes at room temperature. The mixture was adjusted to about pH 10 with aqueous sodium hydroxide solution (10%) and extracted with ethyl acetate (25 ml×3). The combined organic extracts were washed with saturated brine (25 ml), dried over anhydrous magnesium sulfate, filtered to remove the drying agent and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound 5-(2-diethylamino-ethyl)-3-methyl-4-oxo-4,5,6,7,8,9-hexahydro-1H-1,5-diaza-cyclopentacyclooctene-2-carbaldehyde 60e (60 mg, yield 26.7%) as a white solid.

Workup

  1. additionUpon completion of the addition
  2. stirringthe reaction mixture was stirred for 30 minutes at room temperature
  3. temperatureheated
  4. temperatureto reflux for 2 hours in an oil bath
  5. temperaturerefluxed for another 7 hours
  6. customthe reaction mixture was quenched with water
  7. additionadded with hydrochloric acid solution (1 ml, 2 mol/L)
  8. stirringstirred for 30 minutes at room temperature
  9. extractionextracted with ethyl acetate (25 ml×3)
  10. washThe combined organic extracts were washed with saturated brine (25 ml)
  11. dry with materialdried over anhydrous magnesium sulfate
  12. filtrationfiltered
  13. customto remove the drying agent
  14. concentrationconcentrated under reduced pressure
  15. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-822eaec074fc409bbaca46aaad104ade
Source dataset
uspto-grants-2012_12
Patent number
US08329682B2

Reaction notes

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