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

HRID 906046Notes

Reaction equation

HRID 906046 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[OH:21][C:22]1[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][CH:23]=1.CN1CCOCC1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C>[OH:21][C:22]1[CH:30]=[CH:29][C:25]([C:26]([NH:1][C:2]2[CH:7]=[CH:6][C:5]([N:8]3[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]3)=[CH:4][CH:3]=2)=[O:27])=[CH:24][CH:23]=1

Participants

6

Reactant 4

HCID 1354-Hydroxybenzoic AcidHCID 79724-MethylmorpholineHCID 2724699PyBOPHCID 11011301tert-Butyl 4-(4-aminophenyl)piperazine-1-carboxylate

Product 1

HCID 54019812Tert-butyl 4-{4-[(4-hydroxybenzoyl)amino]phenyl}piperazine-1-carboxylateYield 24%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of tert-butyl 4-(4-aminophenyl)piperazine-1-carboxylate (1 eq), 4-hydroxybenzoic acid (1.1 eq), N-methylmorpholine (3 eq) in dry DMF (0.16 M), was added PyBop (1.5 eq). The reaction mixture was heated at 60° C. with stirring for 60 h. At this time the reaction was allowed to cool to RT partitioned between EtOAc and 1N aqueous HCl. The aqueous fraction was extracted with EtOAc and the combined organics washed with saturated aqueous Na2CO3, brine, before being dried over Na2SO4, filtered and evaporated in vacuo. Purification was by flash chromatography on silica gel (4:6) EtOAc/PE) to afford the title compound (24%).

Workup

  1. temperatureto cool to RT
  2. custompartitioned between EtOAc and 1N aqueous HCl
  3. extractionThe aqueous fraction was extracted with EtOAc
  4. washthe combined organics washed with saturated aqueous Na2CO3, brine
  5. dry with materialbefore being dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customPurification

Sources & evidence

ORD record
ord-d98d7e3d44304e96852ff05aaa8aa53a
Source dataset
uspto-grants-2011_09
Patent number
US08012982B2

Reaction notes

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