1-Hydroxybenzotriazole → HCID 23078913, compound

HRID 1869007Notes

Reaction equation

HRID 1869007 reaction equation
[CH3:1][C:2]([CH3:11])([C:8]([O-:10])=O)[C:3]([O:5][CH2:6][CH3:7])=[O:4].[CH2:12]([O:19][C:20]([N:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)=[O:21])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.O.C(N(CC)CC)C>[CH2:12]([O:19][C:20]([N:22]1[CH2:27][CH2:26][N:25]([C:8](=[O:10])[C:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])([CH3:1])[CH3:11])[CH2:24][CH2:23]1)=[O:21])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 643495Benzyl piperazine-1-carboxylateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22005575HCID 22005575, compound

Product 1

HCID 23078913HCID 23078913, compoundYield 78%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of diethyl dimethylmalonate (3 g) in ethanol (5 mL) was added a solution of sodium hydroxide (0.64 g) in water (2 mL), and the mixture was stirred at room temperature for 5 days. The reaction mixture was concentrated under reduced pressure, and the residue was acidified by addition of 2 mol/L hydrochloric acid. The resulting mixture was extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to give mono-ethyl dimethylmalonate (2.43 g). To a solution of the obtained mono-ethyl dimethylmalonate (1 g) in N,N-dimethylformamide (20 mL) were added 1-(benzyloxycarbonyl)piperazine (1.38 g), 1-hydroxybenzotriazole (0.93 g), triethylamine (1.31 mL) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (2.4 g), and the mixture was stirred at room temperature for 2 days. The reaction mixture was poured into water, and the resulting mixture was extracted with diethyl ether. The extract was washed with a saturated aqueous sodium hydrogen carbonate solution, water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=4/1-2/1) to give 1-benzyloxycarbonyl-4-[2-ethoxycarbonyl-2-(methyl)propionyl]piperazine (1.77 g). This material was dissolved in ethanol (5 mL). To the solution was added 2 mol/L aqueous sodium hydroxide solution (2.93 mL), and the mixture was stirred at 55° C. overnight. The reaction mixture was poured into water, and the resulting mixture was washed with diethyl ether. The aqueous layer was acidified by addition of 2 mol/L hydrochloric acid, and the mixture was extracted with diethyl ether. The extract was washed with brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to give the title compound (0.28 g).

Workup

  1. extractionthe resulting mixture was extracted with diethyl ether
  2. washThe extract was washed with a saturated aqueous sodium hydrogen carbonate solution, water and brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was removed under reduced pressure
  5. customthe residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=4/1-2/1)

Sources & evidence

ORD record
ord-45368525d21e4682980d97c8b5d59765
Source dataset
uspto-grants-2009_12
Patent number
US07635684B2

Reaction notes

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