Triethylamine → 2-(Methoxycarbonyl)-5-nitrophenyl 4-methylpiperazine-1-carboxylate

HRID 2109797Notes

Reaction equation

HRID 2109797 reaction equation
[CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[CH:6][C:5]=1[OH:13].ClC(Cl)(O[C:19](=[O:25])OC(Cl)(Cl)Cl)Cl.C(N(C(C)C)CC)(C)C.CCN(CC)CC.[CH3:43][N:44]1[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]1>C1COCC1.C(Cl)Cl>[CH3:43][N:44]1[CH2:49][CH2:48][N:47]([C:19]([O:13][C:5]2[CH:6]=[C:7]([N+:10]([O-:12])=[O:11])[CH:8]=[CH:9][C:4]=2[C:3]([O:2][CH3:1])=[O:14])=[O:25])[CH2:46][CH2:45]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 531671-MethylpiperazineHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 139539Salicylic acid, 4-nitro-, methyl ester

Product 1

HCID 576329252-(Methoxycarbonyl)-5-nitrophenyl 4-methylpiperazine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a dry flask are added 2-hydroxy-4-nitro-benzoic acid methyl ester (40 mmol) (from Example 1h) and triphosgene (26.6 mmol) and DCM (100 mL). The reaction mixture is cooled to 0° C. and diisopropylethylamine (40 mmol) is added slowly. After addition the mixture is warmed to rt. After 1 h at this temperature it is refluxed for 1 h. The mixture is cooled down and the solvents are removed. THF (100 mL), Et3N (80 mmol), and N-methyl piperazine (80 mmol) are added and the mixture is stirred at rt overnight. The solvent is removed and the residue dissolved in EtOAc. Phases are separated upon addition of a 10% solution of NaHCO3. The organic phase is washed with brine, dried on Na2SO4 and evaporated. The crude is used in the following reaction.

Workup

  1. additionAfter addition the mixture
  2. temperatureis warmed to rt
  3. temperatureAfter 1 h at this temperature it is refluxed for 1 h
  4. temperatureThe mixture is cooled down
  5. customthe solvents are removed
  6. customThe solvent is removed
  7. dissolutionthe residue dissolved in EtOAc
  8. customPhases are separated upon addition of a 10% solution of NaHCO3
  9. washThe organic phase is washed with brine
  10. customdried on Na2SO4
  11. customevaporated
  12. customThe crude is used in the following reaction

Sources & evidence

ORD record
ord-7103a45c34b04e59bb6e01147ce019d9
Source dataset
uspto-grants-2009_04
Patent number
US07514447B2

Reaction notes

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