Hydrazine hydrate (1:1) → (S)-3-[[[2-(benzoylamino)-3-phenylpropyl]ethoxyphosphinyl]amino]-2-oxo-1-piperidineacetic acid, ethyl ester

HRID 484765Notes

Reaction equation

HRID 484765 reaction equation
C1(=O)[N:5]([CH:6]([CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:7][P:8]([NH:13][C@H:14]2[CH2:19][CH2:18][CH2:17][N:16]([CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])[C:15]2=[O:26])([O:10][CH2:11][CH3:12])=[O:9])[C:4](=[O:34])[C:3]2=[CH:35][CH:36]=[CH:37][CH:38]=[C:2]12.O.NN>O1CCOCC1>[C:4]([NH:5][CH:6]([CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:7][P:8]([NH:13][C@H:14]1[CH2:19][CH2:18][CH2:17][N:16]([CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])[C:15]1=[O:26])([O:10][CH2:11][CH3:12])=[O:9])(=[O:34])[C:3]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:2]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 86740219(S)-3-[[[2-phthalimido-3-phenylpropyl]ethoxyphosphinyl]amino]-2-oxo-1-piperidineacetic acid, ethyl ester

Product 1

HCID 86740220(S)-3-[[[2-(benzoylamino)-3-phenylpropyl]ethoxyphosphinyl]amino]-2-oxo-1-piperidineacetic acid, ethyl ester

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of (S)-3-[[[2-phthalimido-3-phenylpropyl]ethoxyphosphinyl]amino]-2-oxo-1-piperidineacetic acid, ethyl ester in dioxane is treated with hydrazine hydrate and stirred for 24 hours at room temperature. The mixture is then partitioned between ethyl acetate-water and the ethyl acetate phase is washed with water and saturated sodium chloride, dried (Na2SO4), and evaporated. The residue is taken up in dry toluene and refluxed for one hour. The mixture is filtered, treated with triethylamine and benzoyl chloride and stirred at room temperature for 30 minutes. The mixture is diluted with ethyl acetate, washed successively with 5% potassium bisulfate, saturated sodium bicarbonate, and saturated sodium chloride, dried (Na2SO4), and evaporated. The residue is chromatographed on silica gel to give (S)-3-[[[2-(benzoylamino)-3-phenylpropyl]ethoxyphosphinyl]amino]-2-oxo-1-piperidineacetic acid, ethyl ester.

Workup

  1. customThe mixture is then partitioned between ethyl acetate-water
  2. washthe ethyl acetate phase is washed with water and saturated sodium chloride
  3. dry with materialdried (Na2SO4)
  4. customevaporated
  5. temperaturerefluxed for one hour
  6. filtrationThe mixture is filtered
  7. additiontreated with triethylamine and benzoyl chloride
  8. stirringstirred at room temperature for 30 minutes
  9. additionThe mixture is diluted with ethyl acetate
  10. washwashed successively with 5% potassium bisulfate, saturated sodium bicarbonate, and saturated sodium chloride
  11. dry with materialdried (Na2SO4)
  12. customevaporated
  13. customThe residue is chromatographed on silica gel

Sources & evidence

ORD record
ord-c0035dbb0b4f4490b838651e9b1dbf5a
Source dataset
uspto-grants-1985_08
Patent number
US04533661

Reaction notes

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