Hydrochloric Acid → Diethyl 2-(4-(piperazin-1-yl)benzyl)-2-methylmalonate

HRID 1896275Notes

Reaction equation

HRID 1896275 reaction equation
[NH2:1][C:2]1[CH:20]=[CH:19][C:5]([CH2:6][C:7]([CH3:18])([C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:4][CH:3]=1.Cl[CH2:22][CH2:23][NH:24][CH2:25][CH2:26]Cl.Cl>C1(C)C(C)=CC=CC=1>[N:1]1([C:2]2[CH:3]=[CH:4][C:5]([CH2:6][C:7]([CH3:18])([C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:19][CH:20]=2)[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 9533Bis(2-chloroethyl)amineHCID 54055855Diethyl methyl-(4-amino)benzylmalonate

Product 1

HCID 67382829Diethyl 2-(4-(piperazin-1-yl)benzyl)-2-methylmalonateYield 76.3%

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent

Procedure

A solution of diethyl 2-(4-aminobenzyl)-2-methylmalonate (2.00 g, 7.17 mmol) and Bis-(2-chloroethyl) amine.HCl (1.90 g, 10.8 mmol) in xylene (10 ml) were heated at reflux for 48 h. The reaction mixture was concentrated and the residue was partitioned between saturated sodium bicarbonate solution and ethyl acetate. The separated organic layer was washed with water, brine solution, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give the crude product. Purification by column chromatography over neutral alumina using 5% methanol in CHCl3 as eluent afforded 1.90 g (76.3%) of diethyl 2-(4-(piperazin-1-yl)benzyl)-2-methylmalonate as brown oil.

Workup

  1. temperatureat reflux for 48 h
  2. concentrationThe reaction mixture was concentrated
  3. customthe residue was partitioned between saturated sodium bicarbonate solution and ethyl acetate
  4. washThe separated organic layer was washed with water, brine solution
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give the crude product
  9. customPurification by column chromatography over neutral alumina using 5% methanol in CHCl3 as eluent

Sources & evidence

ORD record
ord-911eed60660345f2817c2aeec12b8d19
Source dataset
uspto-grants-2013_08
Patent number
US08518948B2

Reaction notes

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