o-Phenylbenzoic acid → HCID 66931936, compound

HRID 2196188Notes

Reaction equation

HRID 2196188 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][C:15]=2[F:21])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:22]1([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:23]([C:28](O)=[O:29])=[CH:24][CH:25]=[CH:26][CH:27]=1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl.[OH-].[Na+]>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:28]([C:23]3[C:22]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)=[CH:27][CH:26]=[CH:25][CH:24]=3)=[O:29])=[CH:16][C:15]=2[F:21])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 70357o-Phenylbenzoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 162036301,1-Dimethylethyl 4-(4-amino-2-fluorophenyl)-1-piperazinecarboxylate

Product 1

HCID 66931936HCID 66931936, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 14798Sodium HydroxideSolvent

Procedure

To a solution of 4-(4-Amino-2-fluoro-phenyl)-piperazine-1-carboxylic acid tert-butyl ester (0.50 g, 1.7 mmol) and biphenyl-2-carboxylic acid (0.38 g, 1.9 mmol) in CH2Cl2 (30 mL) was added 1-hydroxybenzotriazole hydrate (0.27 g, 2.0 mmol), and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.38 g, 2.0 mmol). After stirring at room temperature for 18 h, the reaction was diluted with 1 N NaOH (50 mL) and extracted with CH2Cl2 (3×50 mL). The organic extracts were combined, dried (Na2SO4), and concentrated. Chromatography of the resulting residue (SiO2: EtOAc/hexanes) yielded 4-{4-[(biphenyl-2-carbonyl)-amino]-2-fluoro-phenyl}-piperazine-1-carboxylic acid tert-butyl ester, which was further dissolved in MeOH (20 mL) and 4N HCl in dioxanes. After stirring for 5 h, the reaction mixture was concentrated down, neutralized with 1N NaOH, and extracted with EtOAc (3×75mL). The orgranic extracts were combined, dried (Na2SO4), and the solvent was evaporated under reduced pressure to yield the title compound.

Workup

  1. extractionextracted with CH2Cl2 (3×50 mL)
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-f610e0172365402e9746d49a4500921b
Source dataset
uspto-grants-2012_12
Patent number
US08338426B2

Reaction notes

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