Sodium Hydroxide → HCID 57494065, compound

HRID 1842349Notes

Reaction equation

HRID 1842349 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+].[C:14]([O:18][C:19]([O:21]C(OC(C)(C)C)=O)=O)([CH3:17])([CH3:16])[CH3:15].[CH3:29][S:30](Cl)(=[O:32])=[O:31]>O1CCOCC1.O.C(N(CC)CC)C>[C:14]([O:18][C:19]([N:6]1[CH2:7][CH2:8][N:3]([S:30]([CH3:29])(=[O:32])=[O:31])[CH:4]([C:9]([OH:11])=[O:10])[CH2:5]1)=[O:21])([CH3:17])([CH3:16])[CH3:15]

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 31297Methanesulfonyl chlorideHCID 90495Di-tert-butyl dicarbonateHCID 2723757Piperazine-2-carboxylic acid dihydrochloride

Product 1

HCID 57494065HCID 57494065, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8471TriethylamineSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

Amine preparation: To a suspension of piperazine-2-carboxylic acid dihydrochloride (10.0 g) in 1,4-dioxane (100 mL) and water (50 mL), cooled down to 0° C., was slowly added 17M sodium hydroxide solution (8.6 mL) followed by di-tert-butyldicarbonate (11.8 g). The reaction mixture was warmed to room temperature and stirred for 5 h. Triethylamine (13.7 mL) followed by methanesulfonyl chloride (3.8 mL) was then added. After stirring for 24 h the reaction mixture was concentrated down, the residue diluted with ethyl acetate, washed with 2M hydrochloric acid, brine, dried (MgSO4) and the solvent removed in vacuo to yield crude 4-methanesulfonyl-piperazine-1,3-dicarboxylic acid 1-tert-butyl ester (8.46 g). This was subsequently dissolved in DMF (50 mL), and was treated with added potassium carbonate (7.5 g) and iodomethane (8.5 mL). After stirring for 24 h the reaction mixture was diluted with ethyl acetate, washed with water, brine, dried (MgSO4) and the solvent removed in vacuo. The residue was purified by flash chromatography to yield 4-methanesulfonyl-piperazine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (3.27 g).

Workup

  1. temperatureThe reaction mixture was warmed to room temperature
  2. additionwas then added
  3. stirringAfter stirring for 24 h the reaction mixture
  4. concentrationwas concentrated down
  5. additionthe residue diluted with ethyl acetate
  6. washwashed with 2M hydrochloric acid, brine
  7. dry with materialdried (MgSO4)
  8. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-f13bc072e08e4689a0933c9f29a03fd8
Source dataset
uspto-grants-2015_02
Patent number
US08946217B2

Reaction notes

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