Benzyl chloroformate → 1-Benzyl 4-tert-butyl 2-phenylpiperazine-1,4-dicarboxylate

HRID 473816Notes

Reaction equation

HRID 473816 reaction equation
[C:1]1([CH:7]2[NH:12][CH2:11][CH2:10][N:9]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[C:21]([O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:22].C(N(C(C)C)CC)(C)C>O1CCOCC1.C(OCC)(=O)C>[C:1]1([CH:7]2[CH2:8][N:9]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:10][CH2:11][N:12]2[C:21]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[O:22])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 3

HCID 10387Benzyl chloroformateHCID 81531DiisopropylethylamineHCID 2735358Tert-butyl 3-phenylpiperazine-1-carboxylate

Product 1

HCID 675145701-Benzyl 4-tert-butyl 2-phenylpiperazine-1,4-dicarboxylateYield 59%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of tert-butyl 3-phenylpiperazine-1-carboxylate (0.95 g, 3.6 mmol), benzyl chloroformate (0.85 g, 5.0 mmol) and diisopropylethylamine (1.0 g, 7.7 mmol) in dioxane (20 mL) was heated to 95° C. for 3 hours. After cooling, the reaction mixture was diluted with ethyl acetate (100 mL), and washed with saturated aqueous sodium bicarbonate (50 mL) and brine (25 mL). After drying over anhydrous sodium sulfate, filtration and concentration, the residue was purified by silica gel column chromatography (ethyl acetate/hexanes, 1:8) to give 1-benzyl 4-tert-butyl 2-phenylpiperazine-1,4-dicarboxylate (0.84 g, 59% yield).

Workup

  1. temperatureAfter cooling
  2. washwashed with saturated aqueous sodium bicarbonate (50 mL) and brine (25 mL)
  3. dry with materialAfter drying over anhydrous sodium sulfate, filtration and concentration
  4. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexanes, 1:8)

Sources & evidence

ORD record
ord-80e881508e534ff1bce91a395aef24fb
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

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