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

HRID 2191422Notes

Reaction equation

HRID 2191422 reaction equation
C([O:3][C:4]([C:6]1[C:7]([CH3:30])=[C:8]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[NH:9][C:10]=1[CH2:11][CH2:12][CH2:13][NH:14][CH2:15][CH2:16][N:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1)=O)C.C[Al](C)C>C1(C)C=CC=CC=1>[C:26]([O:25][C:23]([C:8]1[NH:9][C:10]2[CH2:11][CH2:12][CH2:13][N:14]([CH2:15][CH2:16][N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)[C:4](=[O:3])[C:6]=2[C:7]=1[CH3:30])=[O:24])([CH3:29])([CH3:28])[CH3:27]

Participants

4

Reactant 2

HCID 16682925TrimethylaluminumHCID 592500493-methyl-5-[3-(2-morpholin-4-yl-ethylamino)-propyl]-1H-pyrrole-2,4-dicarboxylic acid 2-tert-butyl ester 4-ethyl ester

Product 1

HCID 592500943-Methyl-5-(2-morpholin-4-yl-ethyl)-4-oxo-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carboxylic acid tert-butyl esterYield 61%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

3-Methyl-5-[3-(2-morpholin-4-yl-ethylamino)-propyl]-1H-pyrrole-2,4-dicarboxylic acid 2-tert-butyl ester 4-ethyl ester 10a (2.238 g, 5.29 mmol) was dissolved in 50 ml of toluene under stirring, and added slowly with a solution of trimethyl aluminum in toluene (3.9 ml, 2 mol/L, 7.9 mmol) under an argon atmosphere. The reaction system was stirred for 30 minutes at room temperature until no white smoke was released, and refluxed for another 3 hours in an oil bath. After thin lay chromatography showed the disappearance of starting materials, the oil bath was removed, and the reaction mixture was quenched with a little water, adjusted to pH 8-10 with dilute sodium hydroxide solution (2 mol/L), added with saturated brine (50 ml) and extracted with ethyl acetate (50 ml×3). The combined organic extracts were filtered through a pad of Celite, concentrated under reduced pressure to obtain the title compound 3-methyl-5-(2-morpholin-4-yl-ethyl)-4-oxo-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-c]azepine-2-carboxylic acid tert-butyl ester 10b (1.218 g, yield 61%) as a light yellow solid

Workup

  1. stirringThe reaction system was stirred for 30 minutes at room temperature until no white smoke
  2. temperaturerefluxed for another 3 hours in an oil bath
  3. customthe oil bath was removed
  4. customthe reaction mixture was quenched with a little water
  5. additionadded with saturated brine (50 ml)
  6. extractionextracted with ethyl acetate (50 ml×3)
  7. filtrationThe combined organic extracts were filtered through a pad of Celite
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c3da1a5d64d54453b6b95ac53b3d5239
Source dataset
uspto-grants-2012_12
Patent number
US08329682B2

Reaction notes

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