N-carbobenzyloxyalanine → benzyloxycarbonyl-L-alanyl-2-[1-(2,4-dimethoxybenzyl)-2,5-dioxopyrrolidin-3-yl] glycine methyl ester

HRID 358307Notes

Reaction equation

HRID 358307 reaction equation
[CH3:1][O:2][C:3](=[O:24])[CH:4]([CH:6]1[CH2:10][C:9](=[O:11])[N:8]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][C:14]=2[O:21][CH3:22])[C:7]1=[O:23])[NH2:5].[CH2:25]([O:32][C:33]([NH:35][C@H:36]([C:38](O)=[O:39])[CH3:37])=[O:34])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>CN(C)C=O>[CH3:1][O:2][C:3](=[O:24])[CH:4]([CH:6]1[CH2:10][C:9](=[O:11])[N:8]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][C:14]=2[O:21][CH3:22])[C:7]1=[O:23])[NH:5][C:38](=[O:39])[C@H:36]([CH3:37])[NH:35][C:33]([O:32][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:34]

Participants

4

Reactant 2

HCID 736104N-carbobenzyloxyalanineHCID 131053912-[1-(2,4-Dimethoxybenzyl)-2,5-dioxopyrrolidin-3-yl]glycine methyl ester

Product 1

HCID 70503176benzyloxycarbonyl-L-alanyl-2-[1-(2,4-dimethoxybenzyl)-2,5-dioxopyrrolidin-3-yl] glycine methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In 20 ml of dimethylformamide were dissolved 1 g of 2-[1-(2,4-dimethoxybenzyl)-2,5-dioxopyrrolidin-3-yl] glycine methyl ester and 1.5 g of N-hydroxysuccinimide ester of benzyloxycarbonyl-L-alanine, and the solution was stirred at room temperature for 50 hours. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in ethyl acetate, washed with 2 N hydrochloric acid and saturated sodium hydrogen carbonate, and dried over sodium sulfate and concentrated under reduced pressure. To the residue was added petroleum ether to give benzyloxycarbonyl-L-alanyl-2-[1-(2,4-dimethoxybenzyl)-2,5-dioxopyrrolidin-3-yl] glycine methyl ester as a white powder. This powder was dissolved in a mixture of 50 ml of methanol and 10 ml of acetic acid and stirred with 500 ml of palladium black in a stream of hydrogen at room temperature for 3 hours. The catalyst was filtered off and the filtrate was concentrated under reduced pressure. The residue was dried in a desiccator overnight and dissolved in 50 ml of methanol. With adjusting pH to 9-10 with 1 N sodium hydroxide, the solution was stirred at room temperature for 3 hours. This reaction mixture was adjusted to pH 5 and concentrated under reduced pressure. The residue was dried in a desiccator overnight, dissolved in 10 ml of a 30% solution of hydrogen bromide in acetic acid, and stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in water and adjusted to pH 4 with saturated sodium hydrogen carbonate. It was chromatographed on a column (200 ml) of MCI gel CHP-20P, and water to 50% aqueous methanol-water gradient elution was carried out. The eluate was concentrated under reduced pressure and lyophilized to give L-alanyl-2-(2,5-dioxopyrrolidin-3-yl)glycine as a white powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in ethyl acetate
  3. washwashed with 2 N hydrochloric acid and saturated sodium hydrogen carbonate
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. additionTo the residue was added petroleum ether

Sources & evidence

ORD record
ord-a78a45837d054101a6fbd897dae8f185
Source dataset
uspto-grants-1984_08
Patent number
US04465844

Reaction notes

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