N-Benzylnormechlorethamine → HCID 59509446, compound

HRID 2407480Notes

Reaction equation

HRID 2407480 reaction equation
C(=O)([O-])[O-].[K+].[K+].[CH2:7]([N:14]([CH2:18][CH2:19]Cl)[CH2:15][CH2:16]Cl)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[C:21]([O:29][CH2:30][CH3:31])(=[O:28])[CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[CH2:30]([O:29][C:21]([C:22]1([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:19][CH2:18][N:14]([CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:15][CH2:16]1)=[O:28])[CH3:31]

Participants

6

Reactant 3

HCID 5928N-BenzylnormechlorethamineHCID 7761Diethyl MalonateHCID 11430Potassium Carbonate

Product 1

HCID 59509446HCID 59509446, compound

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Potassium carbonate (79.22 g, 0.572 mol) and tetrabutylammonium bromide (6.16 g, 0.019 mol) are added to a solution of benzyl-bis-(2-chloroethyl)amine (47.5 g, 0.205 mol) and diethyl malonate (30.62 g, 0.191 mol) in N,N-dimethylformamide (450 mL). The reaction mixture is heated at 80° C. for 1.5 hours and then concentrated under reduced pressure. The residue is treated with demineralized water (200 mL) and the aqueous layer is extracted with ethyl acetate (3×100 mL). Combined organic layers are washed with brine (1×40 mL) and dried over sodium sulphate. Removal of solvent gives a viscous liquid which is purified by column chromatography (silica gel 230-400 mesh, n-hexane:ethyl acetate 80:20) to give 1-benzylpiperidine-4,4-dicarboxylic acid diethyl ester.

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionThe residue is treated with demineralized water (200 mL)
  3. extractionthe aqueous layer is extracted with ethyl acetate (3×100 mL)
  4. washCombined organic layers are washed with brine (1×40 mL)
  5. dry with materialdried over sodium sulphate
  6. customRemoval of solvent
  7. customgives a viscous liquid which
  8. customis purified by column chromatography (silica gel 230-400 mesh, n-hexane:ethyl acetate 80:20)

Sources & evidence

ORD record
ord-e9e28af586f9448abb5a5b92e696b543
Source dataset
uspto-grants-2014_08
Patent number
US08809539B2

Reaction notes

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