Hydrochloric Acid → Diethyl 2-methyl-2-(4-(piperazin-1-yl)phenyl)malonate

HRID 1896270Notes

Reaction equation

HRID 1896270 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:19])([C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:4][CH:3]=1.Cl[CH2:21][CH2:22][NH:23][CH2:24][CH2:25]Cl.Cl>C1(C)C(C)=CC=CC=1>[CH3:19][C:8]([C:5]1[CH:6]=[CH:7][C:2]([N:1]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)=[CH:3][CH:4]=1)([C:9]([O:11][CH2:12][CH3:13])=[O:10])[C:14]([O:16][CH2:17][CH3:18])=[O:15]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 9533Bis(2-chloroethyl)amineHCID 12370795HCID 12370795, compound

Product 1

HCID 67382666Diethyl 2-methyl-2-(4-(piperazin-1-yl)phenyl)malonateYield 63.5%

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent

Procedure

A suspension of diethyl 2-(4-aminophenyl)-2-methylmalonate (6.00 g, 22.6 mmol), Bis-(2-chloroethyl) amine.HCl (4.82 g, 27.2 mmol) in xylene (20 ml) was refluxed for 48 h. The reaction mixture was concentrated in vacuo 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 under reduced pressure to afford crude product. Purification by column chromatography over neutral alumina using 5% MeOH in CHCl3 as eluent afford 4.80 g (63.5%) of diethyl 2-methyl-2-(4-(piperazin-1-yl)phenyl)malonate as brown oil.

Workup

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

Sources & evidence

ORD record
ord-1c7ea67d264d417db8234e9a5046e4fe
Source dataset
uspto-grants-2013_08
Patent number
US08518948B2

Reaction notes

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