Hydrazine hydrate (1:1) → Dimethyl 2-aminomethyl-2-(4-tert-butoxycarbonylpiperazin-1-yl)malonate

HRID 472108Notes

Reaction equation

HRID 472108 reaction equation
O.NN.[C:4]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]([CH2:26][N:27]2C(=O)C3C(=CC=CC=3)C2=O)([C:22]([O:24][CH3:25])=[O:23])[C:18]([O:20][CH3:21])=[O:19])[CH2:13][CH2:12]1)=[O:10])([CH3:7])([CH3:6])[CH3:5]>CO>[NH2:27][CH2:26][C:17]([N:14]1[CH2:13][CH2:12][N:11]([C:9]([O:8][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:10])[CH2:16][CH2:15]1)([C:18]([O:20][CH3:21])=[O:19])[C:22]([O:24][CH3:25])=[O:23]

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 67057066Dimethyl 2-(4-tert-butoxycarbonylpiperazin-1-yl)-2-(1,3-dioxo-1,3-dihydroisoindol-2-ylmethyl)malonate

Product 1

HCID 57848700Dimethyl 2-aminomethyl-2-(4-tert-butoxycarbonylpiperazin-1-yl)malonateYield 50%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
-5 °C

Procedure

A solution of 2.9 ml (64 mmol) of hydrazine hydrate in 8 ml of methanol is added to a solution of 27.5 g (58 mmol) of dimethyl 2-(4-tert-butoxycarbonylpiperazin-1-yl)-2-(1,3-dioxo-1,3-dihydroisoindol-2-ylmethyl)malonate in 300 ml of methanol cooled beforehand to −5° C. The reaction medium is stirred at from −5° C. to ambient temperature over the course of 3 h. After evaporation and addition of 300 ml of water, the reaction medium is extracted with ethyl acetate. The organic phases are washed with a saturated aqueous solution of sodium hydrogen carbonate, dried over magnesium sulfate, filtered and evaporated. The residue obtained is purified by chromatography on silica gel, elution being carried out with an 8/2 heptane/ethyl acetate mixture and then an increase in polarity up to a 90/10 ethyl acetate/methanol mixture. 10 g (50%) of dimethyl 2-aminomethyl-2-(4-tert-butoxycarbonylpiperazin-1-yl)malonate are thus obtained in the form of a light oil.

Workup

  1. customAfter evaporation and addition of 300 ml of water
  2. extractionthe reaction medium is extracted with ethyl acetate
  3. washThe organic phases are washed with a saturated aqueous solution of sodium hydrogen carbonate
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue obtained
  8. customis purified by chromatography on silica gel, elution
  9. temperaturean increase in polarity up to a 90/10 ethyl acetate/methanol mixture

Sources & evidence

ORD record
ord-fb53153323824a8082616d8af2f176f7
Source dataset
uspto-grants-2014_01
Patent number
US08633196B2

Reaction notes

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