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

HRID 2202162Notes

Reaction equation

HRID 2202162 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-7908998b2abe432e94c202fbabf466cb
Source dataset
uspto-grants-2016_06
Patent number
US09365529B2

Reaction notes

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