1-Hydroxybenzotriazole → HCID 54291569, compound

HRID 1584763Notes

Reaction equation

HRID 1584763 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:13]([OH:15])=O)[CH:10]([CH3:12])[CH3:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[N:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1>CN(C)C=O.ClCCl>[Cl:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[N:23]1[CH2:28][CH2:27][N:26]([C:13](=[O:15])[C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH:10]([CH3:11])[CH3:12])[CH2:25][CH2:24]1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 83693Boc-L-ValineHCID 4156281-(2-Chlorophenyl)piperazineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 54291569HCID 54291569, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of N-tert-butoxycarbonyl-L-valine (2.27 g, 10 mmol) and 1-(2-chlorophenyl)piperazine (2.00 g, 10 mmol) in N,N-dimethylformamide (50 ml) on an ice bath was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.2 g, 11 mmol) and 1-hydroxybenzotriazole (1.5 g, 11 mmol) in dichloromethane (50 ml) dropwise and the mixture was stirred at room temperature for 15 hours. The dichloromethane was then distilled off under reduced pressure and the residue was extracted with ethyl acetate (200 ml). The ethyl acetate layer was serially washed with 10% aqueous citric acid solution, saturated aqueous sodium hydrogen carbonate solution, and saturated saline in the order mentioned and dried over anhydrous sodium sulfate. The solvent was then distilled off and the residue was purified by silica gel chromatography. Elution with ethyl acetate-n-hexane (1:2, v/v) gave 1,1-dimethylethyl 2-(4-(2-chlorophenyl)piperazinyl)-2-oxo-(s)-1-(2-propyl)ethylcarbamate. After this colorless oil was dissolved in ethyl acetate (50 ml), 4N HCl/ethyl acetate (50ml) was added dropwise under ice-cooling. The mixture was stirred at room temperature for 3 hours. The reaction product was filtered and washed with ethyl acetate-n-hexane (1:1, v/v) to provide 1-((s)-2-amino-3-methyl-1-oxobutyl)-4-(2-chlorophenyl)piperazine hydrochloride (3.32 g, 95.8%) as colorless crystals.

Workup

  1. distillationThe dichloromethane was then distilled off under reduced pressure
  2. extractionthe residue was extracted with ethyl acetate (200 ml)
  3. washThe ethyl acetate layer was serially washed with 10% aqueous citric acid solution, saturated aqueous sodium hydrogen carbonate solution, and saturated saline in the order
  4. dry with materialdried over anhydrous sodium sulfate
  5. distillationThe solvent was then distilled off
  6. customthe residue was purified by silica gel chromatography
  7. washElution with ethyl acetate-n-hexane (1:2

Sources & evidence

ORD record
ord-72491bdc4eda43c182535701cf6949e0
Source dataset
uspto-grants-1999_08
Patent number
US05935959

Reaction notes

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