1-Hydroxybenzotriazole → Tert-butyl 3-[(4-{[(3,4-dichlorophenyl)amino]carbonyl}piperazin-1-yl)carbonyl]piperidine-1-carboxylate

HRID 2371198Notes

Reaction equation

HRID 2371198 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[C:5]([NH:10][C:11]([N:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)=[O:12])[CH:6]=[CH:7][C:8]=1[Cl:9].C(N(CC)C(C)C)(C)C.[C:28]([O:32][C:33]([N:35]1[CH2:40][CH2:39][CH2:38][CH:37]([C:41](O)=[O:42])[CH2:36]1)=[O:34])([CH3:31])([CH3:30])[CH3:29].ON1C2C=CC=CC=2N=N1>ClCCl>[Cl:2][C:3]1[CH:4]=[C:5]([NH:10][C:11]([N:13]2[CH2:18][CH2:17][N:16]([C:41]([CH:37]3[CH2:38][CH2:39][CH2:40][N:35]([C:33]([O:32][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:34])[CH2:36]3)=[O:42])[CH2:15][CH2:14]2)=[O:12])[CH:6]=[CH:7][C:8]=1[Cl:9]

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27356471-((Tert-butoxy)carbonyl)piperidine-3-carboxylic acidHCID 46743200N-(3,4-dichlorophenyl)piperazine-1-carboxamide hydrochloride

Product 1

HCID 57656778Tert-butyl 3-[(4-{[(3,4-dichlorophenyl)amino]carbonyl}piperazin-1-yl)carbonyl]piperidine-1-carboxylateYield 99%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of N-(3,4-dichlorophenyl)piperazine-1-carboxamide hydrochloride (1.0 g) in dichloromethane (100 mL) was added N,N-di-iso-propylethylamine (0.56 mL) at room temperature. After 10 minutes N-[3-(dimethylamino)propyl]-N-ethylcarbodiimide (617 mg) was added followed by 1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid (671 mg) and 1-hydroxybenzotriazole (435 mg). The reaction was stirred overnight at room temperature. The reaction mixture was partitioned between dichloromethane and water and the organic layer was washed with brine. The organic extract was dried over magnesium sulfate and evaporated. The residue was purified by silica column chromatography, eluting with a gradient of 0 to 15% ethyl acetate in hexane to give the title compound as a white foam (1.4 g, 99%).

Workup

  1. customThe reaction mixture was partitioned between dichloromethane and water
  2. washthe organic layer was washed with brine
  3. extractionThe organic extract
  4. dry with materialwas dried over magnesium sulfate
  5. customevaporated
  6. customThe residue was purified by silica column chromatography
  7. washeluting with a gradient of 0 to 15% ethyl acetate in hexane

Sources & evidence

ORD record
ord-bd6947ceb3ac43ccbc8c74cef9637793
Source dataset
uspto-grants-2014_04
Patent number
US08710224B2

Reaction notes

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