Hydrochloric Acid → 1-Piperazinecarboxylic acid, 4-(4-aMinophenyl)-, phenylMethyl ester

HRID 1778946Notes

Reaction equation

HRID 1778946 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[O:17])[CH2:12][CH2:11]2)=[CH:6][CH:5]=1)([O-])=O.[BH4-].[Na+].Cl>CO>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([N:10]2[CH2:11][CH2:12][N:13]([C:16]([O:18][CH2:19][C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)=[O:17])[CH2:14][CH2:15]2)=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 57489618HCID 57489618, compound

Product 1

HCID 574896191-Piperazinecarboxylic acid, 4-(4-aMinophenyl)-, phenylMethyl ester

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a mixture of benzyl 4-(4-nitrophenyl)piperazine-1-carboxylate (I3) (1.11 g, 3.25 mmol) and CoCl2 (0.844 g, 6.50 mmol) in MeOH (30 mL) was added NaBH4 (1.23 g, 32.5 mmol) portion-wise at 0° C. Stirring was continued at 0° C. for 1 hour before aqueous 3 M HCl (10 mL) was added. The mixture was concentrated in vacuo to remove the MeOH and the aqueous layer was extracted twice with diethyl ether. The aqueous layer was basified with 1 M aqueous NaOH and extracted twice with EtOAc. The combined organic extracts were dried (MgSO4), concentrated in vacuo, then adsorbed onto silica gel and purified by silica gel column chromatography (Biotage Isolera, 12 g SiO2 cartridge, 50-60% EtOAc in hexanes) to give the title compound K2 as a purple solid (397 mg, 39%); 1H NMR (400 MHz, CDCl3) δ 7.40-7.29 (m, 5H), 6.83-6.78 (m, 2H), 6.68-6.62 (m, 2H), 5.16 (s, 2H), 3.70-3.61 (m, 4H), 3.46 (s, 2H), 3.10-2.86 (m, 4H). LCMS-A: rt 4.650 min; m/z 312.1 [M+H]+.

Workup

  1. additionwas added
  2. concentrationThe mixture was concentrated in vacuo
  3. customto remove the MeOH
  4. extractionthe aqueous layer was extracted twice with diethyl ether
  5. extractionextracted twice with EtOAc
  6. dry with materialThe combined organic extracts were dried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. custompurified by silica gel column chromatography (Biotage Isolera, 12 g SiO2 cartridge, 50-60% EtOAc in hexanes)

Sources & evidence

ORD record
ord-854f0a7a730e4e658a511c47d8d7dd82
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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