Sodium Hydroxide → tert-Butyl 4-[(4-bromo-3-fluorophenyl)carbonyl]piperazine-1-carboxylate

HRID 1804037Notes

Reaction equation

HRID 1804037 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[F:11].Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.[C:34]([O:38][C:39]([N:41]1[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]1)=[O:40])([CH3:37])([CH3:36])[CH3:35].[OH-].[Na+]>O1CCCC1.C(OCC)(=O)C.O>[C:34]([O:38][C:39]([N:41]1[CH2:46][CH2:45][N:44]([C:6](=[O:8])[C:5]2[CH:9]=[CH:10][C:2]([Br:1])=[C:3]([F:11])[CH:4]=2)[CH2:43][CH2:42]1)=[O:40])([CH3:37])([CH3:35])[CH3:36]

Participants

9

Reactant 5

HCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 143452tert-Butyl piperazine-1-carboxylateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27733414-Bromo-3-fluorobenzoic acid

Product 1

HCID 58484677tert-Butyl 4-[(4-bromo-3-fluorophenyl)carbonyl]piperazine-1-carboxylateYield 90.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-Bromo-3-fluorobenzoic acid (4.38 g) was dissolve in tetrahydrofuran (50 mL), 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (4.6 g), 1-hydroxybenzotriazole 1hydrate (3.24 g) and piperazine-1-carboxylic acid tert-butyl ester (4.47 g) were added, and the mixture was stirred at room temperature. The reaction mixture was poured into water under cooling, 4N aqueous sodium hydroxide solution and ethyl acetate were added and the mixture was extracted with ethyl acetate. The organic layer was washed with 4N aqueous sodium hydroxide solution and saturated brine, then washed with saturated brine, and dried over sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by column chromatography (ethyl acetate:hexane) to give the title compound (7.01 g).

Workup

  1. temperatureunder cooling
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with 4N aqueous sodium hydroxide solution and saturated brine
  4. washwashed with saturated brine
  5. dry with materialdried over sodium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. customThe residue was purified by column chromatography (ethyl acetate:hexane)

Sources & evidence

ORD record
ord-0de74b0409c8409eae669a5434119622
Source dataset
uspto-grants-2013_01
Patent number
US08354401B2

Reaction notes

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