Triethylamine → 1-(Tert-butoxycarbonyl)-4-(3,4-dichlorobenzyl)piperazine

HRID 1250514Notes

Reaction equation

HRID 1250514 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[Cl:10])[CH2:5]Br.[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].C(N(CC)CC)C.[OH-].[Na+]>C(Cl)(Cl)Cl.C(OCC)(=O)C>[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][N:21]([CH2:5][C:4]2[CH:7]=[CH:8][C:9]([Cl:10])=[C:2]([Cl:1])[CH:3]=2)[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:12])[CH3:13]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 143452tert-Butyl piperazine-1-carboxylateHCID 6397264-(Bromomethyl)-1,2-dichlorobenzene

Product 1

HCID 222577251-(Tert-butoxycarbonyl)-4-(3,4-dichlorobenzyl)piperazineYield 100.3%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8857Ethyl AcetateSolvent

Procedure

3,4-Dichlorobenzyl bromide (35.20 g, 150 mmol) was added to a solution of N-(tertbutoxycarbonyl)piperazine (24.84 g, 130 mmol) and triethylamine (20.91 ml, 150 mmol) in chloroform (100 ml) over 30 min. After 1 h, the reaction mixture was diluted with ethyl acetate and the product was precipitated out as the hydrochloride salt by adding 1N aqueous hydrogen chloride solution. The solid product was filtered, washed with water and then resuspended in ethyl acetate. Two equivalents of 1N aqueous sodium hydroxide solution was added and the free amine was extracted into ethyl acetate. The organic layer was separated, dried over magnesium sulfate, filtered and concentrated to provide 1-(tert-butoxycarbonyl)-4-(3,4-dichlorobenzyl)piperazine (45 g).

Workup

  1. customthe product was precipitated out as the hydrochloride salt
  2. additionby adding 1N aqueous hydrogen chloride solution
  3. filtrationThe solid product was filtered
  4. washwashed with water
  5. extractionthe free amine was extracted into ethyl acetate
  6. customThe organic layer was separated
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-2e02e248e452433c96a0d88ed4574e49
Source dataset
uspto-grants-2002_01
Patent number
US06339087B1

Reaction notes

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