Hydrochloric Acid → HCID 21701706, compound

HRID 1596208Notes

Reaction equation

HRID 1596208 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH:5]1[C:10]([O:12]CC)=O)(=[O:3])[CH3:2].Cl.[N:16]([O-:18])=O.[Na+].[OH-].[Na+].[CH2:22]([NH2:29])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>O.CN(C)C=O.[Cl-].[Na+].O.C(OCC)(=O)C>[CH2:22]([NH:29][C:10]([CH:5]1[CH2:6][N:7]([N:16]=[O:18])[CH2:8][CH2:9][N:4]1[C:1](=[O:3])[CH3:2])=[O:12])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

12

Reactant 7

HCID 313Hydrochloric AcidHCID 7504BenzylamineHCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 23668193Sodium NitriteHCID 54444758HCID 54444758, compound

Product 1

HCID 21701706HCID 21701706, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolvent3×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

To a slurry of rac-ethyl 1-acetylpiperazine-2-carboxylate (0.5 g) in water (5 ml) was added concentrated hydrochloric acid (1.5 ml) dropwise below 25° C. A solution of sodium nitrite (380 mg) in water (2 ml) was added dropwise at 0° C. The mixture was stirred at 0° C. for 2 hours. A solution of sodium hydroxide (726 mg) in water (10 ml) was added dropwise at 0° C. The water was evaporated off to give crude rac-1-acetyl-2-carboxy-4-nitrosopiperazine (1.0 g). The crude product, benzylamine (0.6 ml) and 1-hydroxybenzotriazole (1.351 g) in N,N-dimethylformamide (5 ml) was added N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride (1.92 g) at 0° C. The reaction mixture was stirred at ambient temperature for 4 hours. The reaction mixture was poured into the mixture of ethyl acetate and brine. The organic layer was combined, dried over magnesium sulfate, and concentrated to give rac-N-benzyl-1-acetyl-4-nitrosopiperazine-2-carboxamide (655 mg). This product was used for next step without purification.

Workup

  1. customThe water was evaporated off
  2. customto give crude rac-1-acetyl-2-carboxy-4-nitrosopiperazine (1.0 g)
  3. stirringThe reaction mixture was stirred at ambient temperature for 4 hours
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-d36e472a087e4e33a6c0413b1d00d4d9
Source dataset
uspto-grants-2001_09
Patent number
US06291464B1

Reaction notes

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