Benzathine → Ethyl 1,4-dibenzyl-3-oxopiperazine-2-carboxylate

HRID 80506

Reaction equation

[CH2:1]([NH:8][CH2:9][CH2:10][NH:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH:20]([C:26]([O:28]CC)=O)[C:21]([O:23][CH2:24][CH3:25])=[O:22]>C(#N)C.[OH-].[Na+]>[CH2:1]([N:8]1[CH2:9][CH2:10][N:11]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:26](=[O:28])[CH:20]1[C:21]([O:23][CH2:24][CH3:25])=[O:22])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of N,N′-dibenzylethylenediamine (14.12 mL, 60.2 mmol) in acetonitrile (100 mL) was added diethyl bromomalonate (5.14 mL, 30.1 mmol), and the mixture was heated with an oil bath at 90° C. (reflux) for 7 hours. The solvent was evaporated to provide a residue that was dissolved in 1M NaOH (aqueous), and the mixture was extracted with ethyl acetate twice, dried over Na2SO4, and the solvent was evaporated. The crude mixture was purified by silica gel chromatography (Analogix IntelliFlash 280, SF40-150) eluting with 15%-30% ethyl acetate/hexanes to afford the title compound. 1H NMR (500 MHz, DMSO-d6) δ ppm 7.38-7.20 (m, 100H), 4.54 (dd, J=15.0, 154.2, 2H), 4.20-4.10 (m, 2H), 4.03 (q, J=7.1, 1H), 3.96 (s, 1H), 3.61 (dd, J=13.5, 41.7, 2H), 3.27-3.14 (m, 2H), 3.05-2.95 (m, 1H), 2.60-2.52 (m, 1H), 1.23 (t, J=7.1, 3H); MS (ESI+) m/z 353.0 (M+H)+.

Workup

temperature(reflux) for 7 hours
customThe solvent was evaporated
customto provide a residue that
extractionthe mixture was extracted with ethyl acetate twice
dry with materialdried over Na2SO4
customthe solvent was evaporated
customThe crude mixture was purified by silica gel chromatography (Analogix IntelliFlash 280, SF40-150)
washeluting with 15%-30% ethyl acetate/hexanes

Sources & evidence

ORD record: ord-db0d9fb1250f40c7b3788303d58a5c1a
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846663B2

Linked notes

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