Trimethylaluminum → 3-Methyl-4-oxo-5-(2-pyrrolidin-1-yl-ethyl)-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carboxylic acid tert-butyl ester

HRID 2191451Notes

Reaction equation

HRID 2191451 reaction equation
C([O:3][C:4]([C:6]1[C:7]([CH3:29])=[C:8]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[NH:9][C:10]=1[CH2:11][CH2:12][CH2:13][NH:14][CH2:15][CH2:16][N:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1)=O)C.C[Al](C)C>C1(C)C=CC=CC=1>[C:25]([O:24][C:22]([C:8]1[NH:9][C:10]2[CH2:11][CH2:12][CH2:13][N:14]([CH2:15][CH2:16][N:17]3[CH2:21][CH2:20][CH2:19][CH2:18]3)[C:4](=[O:3])[C:6]=2[C:7]=1[CH3:29])=[O:23])([CH3:28])([CH3:27])[CH3:26]

Participants

4

Reactant 2

HCID 16682925TrimethylaluminumHCID 592500823-methyl-5-[3-(2-pyrrolidin-1-yl-ethylamino)-propyl]-1H-pyrrole-2,4-dicarboxylic acid 2-tert-butyl ester 4-ethyl ester

Product 1

HCID 592500843-Methyl-4-oxo-5-(2-pyrrolidin-1-yl-ethyl)-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carboxylic acid tert-butyl esterYield 65%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

3-Methyl-5-[3-(2-pyrrolidin-1-yl-ethylamino)-propyl]-1H-pyrrole-2,4-dicarboxylic acid 2-tert-butyl ester 4-ethyl ester 28a (6.754 g, 16.6 mmol) was dissolved in 150 ml of toluene under stirring, and added slowly with a solution of trimethyl aluminum in toluene (16.6 ml, 2 mol/L, 33.2 mmol) to the solution under an argon atmosphere. The reaction mixture was stirred for 20 minutes at room temperature until no white smoke was released, and refluxed for another 3.5 hours in an oil bath. After thin lay chromatography showed the disappearance of starting materials, the oil bath was removed. The reaction mixture was quenched with little ethanol (95%), added with ethyl acetate (100 ml), filtered through a pad of Celite and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound 3-methyl-4-oxo-5-(2-pyrrolidin-1-yl-ethyl)-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carboxylic acid tert-butyl ester 28b (3.894 g, yield 65%) as a yellow oil.

Workup

  1. stirringThe reaction mixture was stirred for 20 minutes at room temperature until no white smoke
  2. temperaturerefluxed for another 3.5 hours in an oil bath
  3. customthe oil bath was removed
  4. customThe reaction mixture was quenched with little ethanol (95%)
  5. additionadded with ethyl acetate (100 ml)
  6. filtrationfiltered through a pad of Celite
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-9da9535fbc444d03b3bac64b81c3b2e7
Source dataset
uspto-grants-2012_12
Patent number
US08329682B2

Reaction notes

Loading…