1-Hydroxybenzotriazole → 3-[4-(2-Bromo-benzoyl)-piperazin-1-yl]-3-oxo-propionic acid tert-butyl ester

HRID 1665654Notes

Reaction equation

HRID 1665654 reaction equation
C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[C:20]([O:24][C:25]([CH2:27][C:28]([O-:30])=O)=[O:26])([CH3:23])([CH3:22])[CH3:21].[Li+].CCN=C=NCCCN(C)C.Cl.Cl.[Br:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=1[C:52]([N:54]1[CH2:59][CH2:58][NH:57][CH2:56][CH2:55]1)=[O:53]>CN(C=O)C.O>[C:20]([O:24][C:25](=[O:26])[CH2:27][C:28]([N:57]1[CH2:56][CH2:55][N:54]([C:52](=[O:53])[C:47]2[CH:48]=[CH:49][CH:50]=[CH:51][C:46]=2[Br:45])[CH2:59][CH2:58]1)=[O:30])([CH3:21])([CH3:22])[CH3:23]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66625832(2-Bromo-phenyl)-piperazin-1-yl-methanone hydrochlorideHCID 86634609Lithium tert-butoxycarbonyl-acetate

Product 1

HCID 578757933-[4-(2-Bromo-benzoyl)-piperazin-1-yl]-3-oxo-propionic acid tert-butyl esterYield 35.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
10 °C

Procedure

HOBt (585 mg, 4.3 mmol) and DIEA (933 mg, 7.2 mmol) were added to a stirred solution of lithium tert-butoxycarbonyl-acetate (600 mg, 3.6 mmol) in DMF (6 mL). The reaction mixture was cooled to 10° C. and EDCI.HCl (830 mg, 4.3 mmol) followed by (2-bromo-phenyl)-piperazin-1-yl-methanone hydrochloride (1.3 g, 4.3 mmol) were added. The reaction mixture was stirred at room temperature overnight then diluted with water and the product extracted with ethyl acetate. The organic layer was washed with brine solution, dried over Na2SO4 and concentrated. The residue was purified by column chromatography using neutral alumina (3% methanol in chloroform) to afford 530 mg (31%) of 3-[4-(2-bromo-benzoyl)-piperazin-1-yl]-3-oxo-propionic acid tert-butyl ester. LCMS: 412.08 (M+)+, 52.6%, 1H NMR: (DMSO-d6): δ 7.7 (d, 1H), 7.5 (m, 1H), 7.4 (m, 2H), 3.7-3.4 (m, 8H), 3.2-3.1 (m, 2H), 1.4 (s, 9H).

Workup

  1. additionwere added
  2. extractionthe product extracted with ethyl acetate
  3. washThe organic layer was washed with brine solution
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-6c4b7b86438b43648433454512934082
Source dataset
uspto-grants-2011_10
Patent number
US08039463B2

Reaction notes

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