Sodium Hydroxide → N-4-Boc-N-1-Cbz-2-piperazine carboxylic acid

HRID 1260460Notes

Reaction equation

HRID 1260460 reaction equation
Cl.Cl.[NH:3]1[CH2:8][CH2:7][NH:6][CH2:5][CH:4]1[C:9]([OH:11])=[O:10].[OH-].[Na+].[CH3:14][C:15]([O:18][C:19](ON=C(C1C=CC=CC=1)C#N)=[O:20])([CH3:17])[CH3:16].[CH2:32]([O:39][C:40]([O:42]N1C(=O)CCC1=O)=O)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>O1CCOCC1.O1CCOCC1.O>[CH2:32]([O:39][C:40]([N:3]1[CH2:8][CH2:7][N:6]([C:19]([O:18][C:15]([CH3:17])([CH3:16])[CH3:14])=[O:20])[CH2:5][CH:4]1[C:9]([OH:11])=[O:10])=[O:42])[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 83172Benzyl succinimido carbonateHCID 938652-(tert-Butoxycarbonyloxyimino)-2-phenylacetonitrileHCID 2723757Piperazine-2-carboxylic acid dihydrochloride

Product 1

HCID 2756777N-4-Boc-N-1-Cbz-2-piperazine carboxylic acid

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolvent2×HCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

A solution 0.164 M of 2-piperazinecarboxylic acid dihydrochloride in a 1:1 dioxane-water mixture was made basic (pH 11) with 50% aqueous NaOH. A 0.68 M solution of Boc-ON (1.1 eq) in dioxane was added dropwise at RT to the above mixture and the reaction mixture was stirred at RT overnight. The mixture was extracted with Et2O (×3) and acidified with conc. HCl to pH 2. The aqueous layer was extracted with EtOAc (×3). The aqueous solution was basified to pH 10 with 50% NaOH. A 0.59 M solution N-(benzyloxycarbonyloxy)succinimide (1.1 eq.) in dioxane was added to the mixture at 0° C. The reaction mixture was stirred 3 h at RT. Dioxane was removed under reduced pressure. The basic solution was extracted with Et2O (×2) then acidified to pH 1 with conc. HCl, and extracted with EtOAc (×3). The combined organic layers were dried and evaporated. The residue was used as such in next step.

Workup

  1. extractionThe mixture was extracted with Et2O (×3)
  2. extractionThe aqueous layer was extracted with EtOAc (×3)
  3. stirringThe reaction mixture was stirred 3 h at RT
  4. customDioxane was removed under reduced pressure
  5. extractionThe basic solution was extracted with Et2O (×2)
  6. extractionextracted with EtOAc (×3)
  7. customThe combined organic layers were dried
  8. customevaporated

Sources & evidence

ORD record
ord-cfbdf6b2666347378471b13b33bd99ba
Source dataset
uspto-grants-2013_06
Patent number
US08470823B2

Reaction notes

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