Benzyl chloroformate → 1,4-Bis(benzyloxycarbonyl)piperazine-2-carboxylic acid

HRID 549656Notes

Reaction equation

HRID 549656 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-:12].[Na+].Cl[C:15]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:16]>O.O1CCOCC1>[CH2:18]([O:17][C:15]([N:3]1[CH2:8][CH2:7][N:6]([C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:12])[CH2:5][CH:4]1[C:9]([OH:11])=[O:10])=[O:16])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

6

Reactant 3

HCID 10387Benzyl chloroformate2×HCID 14798Sodium Hydroxide2×HCID 2723757Piperazine-2-carboxylic acid dihydrochloride

Product 1

HCID 226328591,4-Bis(benzyloxycarbonyl)piperazine-2-carboxylic acidYield 96%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent3×HCID 312751,4-DioxaneSolvent

Procedure

Piperazine-2-carboxylic acid dihydrochloride (10.0 g, 49.2 mmol) was dissolved in H2O (125 mL) and 1,4-dioxane (200 mL), and the solution was brought to pH 11 with 50% NaOH in H2O. Benzyl chloroformate (14 mL, 98 mmol) was added while maintaining the pH at 11 with 50% NaOH in H2O. After 1 h, an additional portion of benzyl chloroformate (2 mL, 14 mmol) was added. After 30 min, the solution was extracted with Et2O (3×100 mL). The aqueous layer was brought to pH 2 with concentrated HCl and extracted with EtOAc (3×200 mL). The combined EtOAc extracts were dried over Na2SO4, filtered, and concentrated under reduced pressure to give 18.9 g (96%) of the desired product as a thick oil. The material was used without further purification. LC-MS: RT=9.250 min; [M+H]+=421.1.

Workup

  1. waitAfter 30 min
  2. extractionthe solution was extracted with Et2O (3×100 mL)
  3. extractionextracted with EtOAc (3×200 mL)
  4. dry with materialThe combined EtOAc extracts were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-56d8a80f3e694a888fbc6e8a4e9a60ef
Source dataset
uspto-grants-2011_05
Patent number
US07943622B2

Reaction notes

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