Piperazine → 4-Fmoc-Piperazine-2-(R)-carboxylic acid

HRID 2354588Notes

Reaction equation

HRID 2354588 reaction equation
Cl.Cl.[NH:3]1[CH2:8][CH2:7][NH:6][CH2:5][C@@H:4]1[C:9]([OH:11])=[O:10].[OH-].[Na+].N1CCNCC1C(O)=O.[C:23](Cl)([O:25][CH2:26][CH:27]1[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[C:33]2[C:28]1=[CH:29][CH:30]=[CH:31][CH:32]=2)=[O:24].N1CCNCC1>O1CCOCC1.O1CCOCC1.O>[CH:38]1[C:39]2[CH:27]([CH2:26][O:25][C:23]([N:6]3[CH2:7][CH2:8][NH:3][C@@H:4]([C:9]([OH:11])=[O:10])[CH2:5]3)=[O:24])[C:28]3[C:33](=[CH:32][CH:31]=[CH:30][CH:29]=3)[C:34]=2[CH:35]=[CH:36][CH:37]=1

Participants

8

Reactant 5

HCID 4837PiperazineHCID 14798Sodium HydroxideHCID 343679-Fluorenylmethyl chloroformateHCID 2723758Piperazine-2-carboxylic acidHCID 12680090(2R)-Piperazine-2-carboxylic acid--hydrogen chloride (1/2)

Product 1

HCID 15018524-Fmoc-Piperazine-2-(R)-carboxylic acidYield 73.4%

Reagents, catalysts & solvents 2

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

Procedure

Piperazine-2(R)-carboxylic acid dihydrochloride (5.95 g) was added to 50 mL dioxane/water (1:1). The solution was cooled in an ice bath and aqueous sodium hydroxide (10% w/v) solution was added drop-wise to adjust the pH to 9˜10. At this pH, piperazine-2-carboxylic acid dissolved completely. Then, Fmoc Chloride (2.46 g) in dioxane was added drop-wise to the ice-cooled solution of piperazine and the reaction mixture was stirred from 0° C. to RT over 5-6 hr. The mixture was poured into 800 ml of ice water and washed once with ether. Then the aqueous phase was acidified to pH 2-3 with 2N of HCl which precipitated a white solid. This solid was filtered and dried in vacuo to obtain 2.46 g of a white powder. MS (ESI pos.): 353 (M+H).

Workup

  1. temperatureThe solution was cooled in an ice bath
  2. washwashed once with ether
  3. customprecipitated a white solid
  4. filtrationThis solid was filtered
  5. customdried in vacuo

Sources & evidence

ORD record
ord-ad1bdd0e88964748b3e548cbd3ffb1db
Source dataset
uspto-grants-2010_07
Patent number
US07754722B2

Reaction notes

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