Diisopropylethylamine → (S)-3-cyclohexyl-2-(2-oxo-4-m-tolyloxy-2,5-dihydro-pyrrol-1-yl)-propionic acid methyl ester

HRID 19281Notes

Reaction equation

HRID 19281 reaction equation
[CH3:1][O:2][C:3](=[O:13])[C@@H:4]([NH2:12])[CH2:5][CH:6]1[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1.C(N(CC)C(C)C)(C)C.C([O:25][C:26](=O)/[CH:27]=[C:28](/[O:31][C:32]1[CH:33]=[C:34]([CH3:38])[CH:35]=[CH:36][CH:37]=1)\[CH2:29]Br)C>CN(C)C=O>[CH3:1][O:2][C:3](=[O:13])[C@@H:4]([N:12]1[CH2:29][C:28]([O:31][C:32]2[CH:33]=[C:34]([CH3:38])[CH:35]=[CH:36][CH:37]=2)=[CH:27][C:26]1=[O:25])[CH2:5][CH:6]1[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 13833920Methyl 3-cyclohexyl-L-alaninateHCID 66895129(E)-4-bromo-3-m-tolyloxy-but-2-enoic acid ethyl ester

Product 1

HCID 66894935(S)-3-cyclohexyl-2-(2-oxo-4-m-tolyloxy-2,5-dihydro-pyrrol-1-yl)-propionic acid methyl esterYield 27.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of (S)-2-amino-3-cyclohexyl-propionic acid methyl ester (1.03 g, 0.006 mol) in N,N-dimethylformamide (8 mL) was added N,N-diisopropylethylamine (3.22 g, 0.025 mol) slowly at room temperature, under nitrogen. The resulting mixture was stirred for 5 min and then treated with (E)-4-bromo-3-m-tolyloxy-but-2-enoic acid ethyl ester (1.50 g, 0.005 mol) and the reaction mixture was heated at 110° C.-120° C. for 16 h. After this time, ice water was added and the resulting mixture was extracted with ethyl acetate. The combined organic layers were washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate and concentrated in vacuo. Purification by flash column chromatography (silica gel (100-200 mesh)) afforded (S)-3-cyclohexyl-2-(2-oxo-4-m-tolyloxy-2,5-dihydro-pyrrol-1-yl)-propionic acid methyl ester (495 mg, 25%) as a yellow oil.

Workup

  1. temperaturethe reaction mixture was heated at 110° C.-120° C. for 16 h
  2. extractionthe resulting mixture was extracted with ethyl acetate
  3. washThe combined organic layers were washed with a saturated aqueous sodium chloride solution
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customPurification by flash column chromatography (silica gel (100-200 mesh))

Sources & evidence

ORD record
ord-b0f60dc95ab9497298320feddeea4170
Source dataset
uspto-grants-2010_06
Patent number
US07741327B2

Reaction notes

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