1-Hydroxybenzotriazole → 2-(N-methoxy-N-methylcarbamoyl)piperazine-1,4-dicarboxylic acid 4-benzyl ester 1-tert-butyl ester

HRID 1006332Notes

Reaction equation

HRID 1006332 reaction equation
Cl.[CH3:2]N(C)CCCN=C=NCC.[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][N:23]([C:26]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[O:27])[CH2:22][C@H:21]1[C:36]([OH:38])=O)=[O:19])([CH3:16])([CH3:15])[CH3:14].[OH:39][N:40]1[C:44]2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>ClCCl>[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][N:23]([C:26]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[O:27])[CH2:22][CH:21]1[C:36](=[O:38])[N:40]([O:39][CH3:2])[CH3:44])=[O:19])([CH3:16])([CH3:15])[CH3:14]

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 70106521-(1,1-Dimethylethyl) 4-(phenylmethyl) (2S)-1,2,4-piperazinetricarboxylate

Product 1

HCID 865896352-(N-methoxy-N-methylcarbamoyl)piperazine-1,4-dicarboxylic acid 4-benzyl ester 1-tert-butyl esterYield 88.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-[3-(Dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (2.11 g) was added over 5 minutes to a mixture of N,0-dimethylhydroxylamine hydrochloride (1.17 g), (2S)-piperazine-1,2,4-tricarboxylic acid 4-benzyl ester 1-tert-butyl ester (3.64 g), 1-hydroxybenzotriazole (1.49 g) and N,N-diisopropylethylamine (2.1 ml) in dichloromethane (40 ml). After being stirred for 18 hours at room temperature, the resulting mixture was extracted with ethyl acetate. The extract was washed with brine, dried over sodium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel using a mixed solvent of hexane and ethyl acetate (3:1) to give 2-(N-methoxy-N-methylcarbamoyl)piperazine-1,4-dicarboxylic acid 4-benzyl ester 1-tert-butyl ester (3.61 g) as a colorless powder.

Workup

  1. extractionthe resulting mixture was extracted with ethyl acetate
  2. washThe extract was washed with brine
  3. dry with materialdried over sodium sulfate
  4. customevaporated under reduced pressure
  5. customThe residue was purified by column chromatography on silica gel using a mixed solvent of hexane and ethyl acetate (3:1)

Sources & evidence

ORD record
ord-6c2323594b184479bcfd0a720d114c35
Source dataset
uspto-grants-2004_09
Patent number
US06787543B2

Reaction notes

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