Diisopropylethylamine → N-{N-[(5-tert-butoxycarbonylthiophen-2-yl)methyl]-N-methyl-L-leucyl}-L-aspartic acid dimethyl ester

HRID 529217Notes

Reaction equation

HRID 529217 reaction equation
[Li+].[C:2]([O:6][C:7]([C:9]1[S:13][C:12]([CH2:14][N:15]([CH3:24])[C@H:16]([C:21]([O-:23])=O)[CH2:17][CH:18]([CH3:20])[CH3:19])=[CH:11][CH:10]=1)=[O:8])([CH3:5])([CH3:4])[CH3:3].Cl.[CH3:26][O:27][C:28](=[O:36])[C@H:29]([CH2:31][C:32]([O:34][CH3:35])=[O:33])[NH2:30].CCN=C=NCCCN(C)C.Cl.O.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>ClCCl>[CH3:26][O:27][C:28](=[O:36])[C@H:29]([CH2:31][C:32]([O:34][CH3:35])=[O:33])[NH:30][C:21](=[O:23])[C@H:16]([CH2:17][CH:18]([CH3:19])[CH3:20])[N:15]([CH2:14][C:12]1[S:13][C:9]([C:7]([O:6][C:2]([CH3:3])([CH3:4])[CH3:5])=[O:8])=[CH:10][CH:11]=1)[CH3:24]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2734892L-Aspartic acid, 1,4-dimethyl ester, hydrochloride (1:1)HCID 27960291-Hydroxybenzotriazole hydrateHCID 90107093N-[(5-tert-butoxycarbonylthiophen-2-yl)methyl]-N-methyl-L-leucine lithium salt

Product 1

HCID 86714699N-{N-[(5-tert-butoxycarbonylthiophen-2-yl)methyl]-N-methyl-L-leucyl}-L-aspartic acid dimethyl esterYield 53.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The compound (0.20 g, 0.58 mmol) obtained in step 2, aspartic acid dimethyl ester hydrochloride (0.12 g, 0.58 mmol), WSC hydrochloride (0.17 g, 0.87 mmol), 1-hydroxybenzotriazole monohydrate (0.090 g, 0.58 mmol), and N,N-diisopropylethylamine (0.39 mL, 2.8 mmol) were dissolved in dichloromethane (5 mL), and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, and ethyl acetate was added. The mixture was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (0.15 g, 0.31 mmol, 53%).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure, and ethyl acetate
  2. additionwas added
  3. washThe mixture was washed with saturated aqueous sodium hydrogen carbonate and saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customthe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-980ce20558f64a81a5fdc025a3bf6337
Source dataset
uspto-grants-2016_05
Patent number
US09346821B2

Reaction notes

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