4-Hydroxybenzoic Acid → Tert-butyl 4-{4-[(4-hydroxybenzoyl)amino]phenyl}piperazine-1-carboxylate

HRID 1459423Notes

Reaction equation

HRID 1459423 reaction equation
[CH3:1][C:2]([CH3:20])([O:4][C:5]([N:7]1[CH2:12][CH2:11][N:10]([C:13]2[CH:19]=[CH:18][C:16]([NH2:17])=[CH:15][CH:14]=2)[CH2:9][CH2:8]1)=[O:6])[CH3:3].[OH:21][C:22]1[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][CH:23]=1.C1CCN(C(Cl)=[N+]2CCCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CCOC(C)=O.C(Cl)Cl>[CH3:3][C:2]([CH3:20])([O:4][C:5]([N:7]1[CH2:12][CH2:11][N:10]([C:13]2[CH:14]=[CH:15][C:16]([NH:17][C:26](=[O:27])[C:25]3[CH:29]=[CH:30][C:22]([OH:21])=[CH:23][CH:24]=3)=[CH:18][CH:19]=2)[CH2:9][CH2:8]1)=[O:6])[CH3:1]

Participants

7

Reactant 4

HCID 1354-Hydroxybenzoic AcidHCID 81531DiisopropylethylamineHCID 11011301tert-Butyl 4-(4-aminophenyl)piperazine-1-carboxylateHCID 15429165Chlorodipiperidinocarbenium hexafluorophosphate

Product 1

HCID 54019812Tert-butyl 4-{4-[(4-hydroxybenzoyl)amino]phenyl}piperazine-1-carboxylateYield 45.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a 100 mL round bottomed flask with a stirring bar and an argon inlet was added 4-(4-(1,1-dimethylethoxycarbonyl)piperazin-1-yl)aniline (0.868 g, 3.13 mmol), 4-hydroxybenzoic acid (0.525 g, 3.80 mmol), chloro-N,N,N',N',-bis(pentamethylene)formamidinium hexafluorophosphate (1.35 g, 3.74 mmol), and CH2Cl2 (45 mL). This mixture was cooled in an ice bath and diisopropylethylamine (0.96 mL, 5.52 mmol) was added. The ice bath was allowed to expire and the mixture was stirred at ambient temperature 18 h. The mixture was diluted with EtOAc and washed with 10% aqueous citric acid, water and brine. Drying (MgSO4), filtration and removal of the solvent in vacuo gave an oil. This material was chromatographed on 100 g of silica gel using 70% EtOAc-hexane as eluant to give 0.57 g of N-(4-(4-(1,1-dimethylethoxycarbonyl)piperazin-1-yl)phenyl)-4-hydroxybenzamide as a grey solid.

Workup

  1. temperatureThis mixture was cooled in an ice bath
  2. washwashed with 10% aqueous citric acid, water and brine
  3. customDrying
  4. filtration(MgSO4), filtration and removal of the solvent in vacuo
  5. customgave an oil
  6. customThis material was chromatographed on 100 g of silica gel using 70% EtOAc-hexane as eluant

Sources & evidence

ORD record
ord-7f744fab07174f798f01c81f3c5e0520
Source dataset
uspto-grants-1998_12
Patent number
US05854245

Reaction notes

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