Hydrochloric Acid → 4-Carbobenzyloxy-l-(4-chloro-2-nitrophenyl)piperazine-2-carboxylic acid

HRID 989042Notes

Reaction equation

HRID 989042 reaction equation
[C:1]([N:11]1[CH2:16][CH2:15][NH:14][CH:13]([C:17]([OH:19])=[O:18])[CH2:12]1)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].C(N(CC(O)=O)CC(O)=O)CN(CC(O)=O)CC(O)=O.[Na][Na].Cl[C:43]1[CH:48]=[C:47](Cl)[CH:46]=[CH:45][C:44]=1[N+:50]([O-:52])=[O:51].C(N(CC)CC)C.[ClH:60]>O.C1C=C(C([N-]C(C2N=CC=CC=2)=O)=O)N=CC=1.O.O.[Cu+2]>[C:1]([N:11]1[CH2:16][CH2:15][N:14]([C:43]2[CH:48]=[CH:47][C:46]([Cl:60])=[CH:45][C:44]=2[N+:50]([O-:52])=[O:51])[CH:13]([C:17]([OH:19])=[O:18])[CH2:12]1)([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 6049Ethylenediaminetetraacetic AcidHCID 8471TriethylamineHCID 118992,4-DichloronitrobenzeneHCID 141233DisodiumHCID 50583624-((Benzyloxy)carbonyl)piperazine-2-carboxylic acid

Product 1

HCID 180047874-Carbobenzyloxy-l-(4-chloro-2-nitrophenyl)piperazine-2-carboxylic acid

Reagents, catalysts & solvents 2

HCID 472011Copper chelateCatalystHCID 962WaterSolvent2×

Conditions

Temperature
80 °C

Procedure

To a solution of 4-carbobenzyloxypiperazine-2-carboxylic acid, copper chelate in 750 ml water was added ethylenediaminetetracetic acid, disodium salt, dihydrate (7.9 g, 21 mmol) and the blue mixture was heated to 80° C. for 3 h. The reaction mixture was cooled to rt and concentrated to dryness. The blue residue was dissolved in 100 ml DMSO. 2,4-dichloronitrobenzene (6.66 g, 35 mmol) and triethyl amine (20 ml, 143 mmol) were added and the solution was heated to 60° C. for 16 h. The dark reaction mixture was cooled to rt. Concentrated HCl was added to pH=3. The solution was then diluted with 500 ml water and the aqueous layer was extracted with ethyl acetate. The combined organics were washed with water, dried over MgSO4 and concentrated to afford 4-carbobenzyloxy-l-(4-chloro-2-nitrophenyl)piperazine-2-carboxylic acid as a yellow residue used directly in the next step.

Workup

  1. temperatureThe reaction mixture was cooled to rt
  2. concentrationconcentrated to dryness
  3. dissolutionThe blue residue was dissolved in 100 ml DMSO
  4. temperaturethe solution was heated to 60° C. for 16 h
  5. customThe dark reaction mixture
  6. temperaturewas cooled to rt
  7. extractionthe aqueous layer was extracted with ethyl acetate
  8. washThe combined organics were washed with water
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-a7be3767bad14644a121357821dc4202
Source dataset
uspto-grants-2003_10
Patent number
US06638934B2

Reaction notes

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