Hydrochloric Acid → Tert-butyl 4-(4-aminobenzoyl)piperazine-1-carboxylate

HRID 1778979Notes

Reaction equation

HRID 1778979 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][CH:3]=1.CCN=C=NCCCN(C)C.Cl.Cl.C1C=CC2N(O)N=NC=2C=1.CCN(CC)CC.[C:41]([N:48]1[CH2:53][CH2:52][NH:51][CH2:50][CH2:49]1)([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42].[OH-].[Na+]>CN(C=O)C.CCOC(C)=O>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:51]2[CH2:50][CH2:49][N:48]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:53][CH2:52]2)=[O:8])=[CH:9][CH:10]=1

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 9784-Aminobenzoic AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 143452tert-Butyl piperazine-1-carboxylateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 2763355Tert-butyl 4-(4-aminobenzoyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-aminobenzoic acid (0.411 g, 3.00 mmol) in DMF (5.0 mL) at room temperature was added EDCl.HCl (0.862 g, 4.50 mmol), HOBt (0.608 g, 4.50 mmol), Et3N (0.835 mL, 6.00 mmol) and N-Boc piperazine (0.671 g, 3.60 mmol). The resulting mixture was stirred at room temperature for 21 hours then 2 M aqueous NaOH was added to adjust the pH to >10. EtOAc was added then the layers separated and the organic layer dried over MgSO4. The volatiles were removed under reduced pressure and the residue was purified by silica gel chromatography (Biotage Isolera, 40 g SiO2 cartridge, 50-90% EtOAc in petroleum benzine 40-60° C.) to give the title compound A21 as a white solid (0.530 g, 56%); LCMS-A: rt 5.079 min; m/z 250.1 [(M-t-Bu)+H]+, 206.1 [(M-Boc)+H]+.

Workup

  1. customthe layers separated
  2. dry with materialthe organic layer dried over MgSO4
  3. customThe volatiles were removed under reduced pressure
  4. customthe residue was purified by silica gel chromatography (Biotage Isolera, 40 g SiO2 cartridge, 50-90% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-d5d9132f07a24003b29f42daf23bf526
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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