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

HRID 517485Notes

Reaction equation

HRID 517485 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-yl-methyl)malonate in 300 ml of methanol previously cooled to −5° C. The reaction medium is stirred from −5° C. to ambient temperature for 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 sulphate, filtered and evaporated. The residue obtained is purified by chromatography over silica gel eluted with an 8/2 heptane/ethyl acetate mixture then the polarity was increased to a 9/1 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 clear 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 sulphate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue obtained
  8. customis purified by chromatography over silica gel
  9. washeluted with an 8/2 heptane/ethyl acetate mixture
  10. temperaturethe polarity was increased to a 9/1 ethyl acetate/methanol mixture

Sources & evidence

ORD record
ord-47e119f7c56b4b138aec3b5ea24ce971
Source dataset
uspto-grants-2015_08
Patent number
US09115102B2

Reaction notes

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