3-tert-Butylaniline → 4-[4-(3-Tert-butyl-phenylcarbamoyl)-phenyl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 2190642Notes

Reaction equation

HRID 2190642 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]([CH:9]=[CH:10][CH:11]=1)[NH2:8])([CH3:4])([CH3:3])[CH3:2].[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][N:22]([C:25]2[CH:30]=[CH:29][C:28]([C:31](O)=[O:32])=[CH:27][CH:26]=2)[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].CCN=C=NCCCN(C)C.Cl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:12]([O:16][C:17]([N:19]1[CH2:20][CH2:21][N:22]([C:25]2[CH:26]=[CH:27][C:28]([C:31](=[O:32])[NH:8][C:7]3[CH:9]=[CH:10][CH:11]=[C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])[CH:6]=3)=[CH:29][CH:30]=2)[CH2:23][CH2:24]1)=[O:18])([CH3:15])([CH3:13])[CH3:14]

Participants

6

Reactant 3

HCID 793343-tert-ButylanilineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27955084-[4-(tert-Butoxycarbonyl)piperazin-1-yl]benzoic acid

Product 1

HCID 593180174-[4-(3-Tert-butyl-phenylcarbamoyl)-phenyl]-piperazine-1-carboxylic acid tert-butyl esterYield 35.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of 3-tert-butyl aniline (117 mg, 0.78 mmol), 4-(4-carboxy-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (prepared as described in Biog. Med. Chem. 2006, 14, 2089) (200 mg, 0.65 mmol), EDCl (375 mg, 0.95 mmol) and a catalytic amount of DMAP in CH2Cl2 was stirred at room temperature overnight. The next day the mixture was partitioned between EtOAc and water. The organic layer was collected, dried over Na2SO4, filtered and concentrated. The residue was chromatographed with silica gel column amd 0-30% EtOAc in hexanes gradient to afford the product (100 mg, Yield: 35%). HRMS m/z calcd for C26H35N3O3 [M+H]+: 438.2751. Found: 438.2753.

Workup

  1. customThe next day the mixture was partitioned between EtOAc and water
  2. customThe organic layer was collected
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was chromatographed with silica gel column amd 0-30% EtOAc in hexanes gradient

Sources & evidence

ORD record
ord-296db7b4338f47059a2aa523136c82ba
Source dataset
uspto-grants-2012_12
Patent number
US08324385B2

Reaction notes

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