Diisopropylethylamine → Tert-butyl 4-(4-(chloromethyl)benzyl)piperazine-1-carboxylate

HRID 1023337Notes

Reaction equation

HRID 1023337 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:14][CH:15](Cl)[C:16]1[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=1.CCN(C(C)C)C(C)C.C([O-])(O)=O.[Na+]>CC#N>[Cl:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][N:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][CH2:10]2)=[CH:18][CH:17]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 516892Sodium BicarbonateHCID 5200171-(Dichloromethyl)-4-methylbenzene

Product 1

HCID 67379301Tert-butyl 4-(4-(chloromethyl)benzyl)piperazine-1-carboxylateYield 47.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a CH3CN (250 mL) solution of piperazine-1-carboxylic acid tert-butyl ester (19.8 g) and alpha,alpha-dichloro-p-xylene (18.6 g) was added DIPEA (18.5 mL) under a N2 atmosphere, then the resultant mixture was stirred at room temperature for 3 days. The reaction mixture was poured into saturated aqueous NaHCO3 (600 mL) and extracted with AcOEt (900 mL). The organic layer was washed with saturated aqueous NaCl (300 mL), dried over anhydrous MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane/AcOEt=3/1) to afford tert-butyl 4-[4-(chloromethyl)benzyl]piperazine-1-carboxylate (16.3 g) as a white powder.

Workup

  1. extractionextracted with AcOEt (900 mL)
  2. washThe organic layer was washed with saturated aqueous NaCl (300 mL)
  3. dry with materialdried over anhydrous MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (n-hexane/AcOEt=3/1)

Sources & evidence

ORD record
ord-6a763e17caf748b19fd18747f6572433
Source dataset
uspto-grants-2014_05
Patent number
US08722663B2

Reaction notes

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