Hydrochloric Acid → HCID 23077829, compound

HRID 1442453Notes

Reaction equation

HRID 1442453 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17](=[O:29])[C:18]([NH:21]C(OC(C)(C)C)=O)([CH3:20])[CH3:19])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl>O1CCCC1>[NH2:21][C:18]([CH3:20])([CH3:19])[C:17]([N:14]1[CH2:15][CH2:16][N:11]([C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:10])[CH2:12][CH2:13]1)=[O:29]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 23077841HCID 23077841, compound

Product 1

HCID 23077829HCID 23077829, compoundYield 96.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-(tert-butoxycarbonylamino)-2-methyl-propionic acid (10 g) in tetrahydrofuran (20 mL) were added 1-(benzyloxycarbonyl)piperazine (16.3 g), 1-hydroxybenzo-triazole (8.02 g) and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (11.4 g), and the mixture was stirred at room temperature overnight. The reaction mixture was poured into water, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. The residue was dissolved in a mixed solvent of n-hexane and ethyl acetate (1/1) (40 mL) at 60° C. with heating, and the solution was stirred at room temperature overnight. To the mixture was added the same solvent (30 mL), and the mixture was further stirred overnight. The precipitated crystals were collected by filtration, and washed with the same solvent and dried under reduced pressure to give 4-benzyloxycarbonyl-1-[2-(tert-butoxycarbonylamino)-2-methylpropionyl]piperazine (13.5 g). To a solution of the obtained 4-benzyloxycarbonyl-1-[2-(tert-butoxycarbonylamino)-2-methylpropionyl]-piperazine (5 g) in tetrahydrofuran (30 mL) was added hydrochloric acid (4 mol/L 1,4-dioxane solution, 40 mL), and the mixture was stirred at room temperature overnight. The precipitated crystals were collected by filtration. The obtained crystals were dissolved in ethyl acetate and a saturated aqueous sodium hydrogen carbonate solution. The organic layer was separated, and the organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give the title compound (3.65 g).

Workup

  1. filtrationThe precipitated crystals were collected by filtration
  2. dissolutionThe obtained crystals were dissolved in ethyl acetate
  3. customThe organic layer was separated
  4. washthe organic layer was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-61d87c04b8ec4e369a7d82e85b6292e1
Source dataset
uspto-grants-2010_02
Patent number
US07655632B2

Reaction notes

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