Carbon Dioxide → Piperazine-1,4-dicarboxylic acid tert-butyl ester 2-fluoro-benzyl ester

HRID 1794064Notes

Reaction equation

HRID 1794064 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[C:14](=[O:16])=[O:15].C(=O)([O-])O.C([N+](CCCC)(CCCC)CCCC)CCC.[F:38][C:39]1[CH:46]=[CH:45][CH:44]=[CH:43][C:40]=1[CH2:41]Cl>C(#N)C>[F:38][C:39]1[CH:46]=[CH:45][CH:44]=[CH:43][C:40]=1[CH2:41][O:15][C:14]([N:11]1[CH2:10][CH2:9][N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH2:13][CH2:12]1)=[O:16]

Participants

6

Reactant 4

HCID 280Carbon DioxideHCID 9580Benzene, 1-(chloromethyl)-2-fluoro-HCID 143452tert-Butyl piperazine-1-carboxylateHCID 110121401-Butanaminium, N,N,N-tributyl-, carbonic acid (1:1)

Product 1

HCID 69142529Piperazine-1,4-dicarboxylic acid tert-butyl ester 2-fluoro-benzyl ester

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

A solution of 4.47 g N-Boc-piperazine in 40 ml acetonitrile was saturated with dry carbon dioxide gas at rt. To this solution was added dropwise in 5 min. a solution of 8.50 g (28 mmol) terabutylammonium hydrogencarbonate (dried at 50° C. at 0.1 mbar for 1 h) in 30 ml acetonitrile, and then carbon dioxide gas bubbled into the stirred solution at rt for 1 h. Then 2.90 g (20 mmol) 2-fluorobenzyl chloride was added drop-wise within 5 min. After stirring at rt for 3 h the reaction mixture was evaporated, 150 ml of water added and extracted with AcOEt. The organic layer was washed with brine, dried over Na2SO4 and evaporated. Purification by flash chromatography on silica gel with hexane/AcOEt 50:50 provided 4.29 g piperazine-1,4-dicarboxylic acid tert-butyl ester 2-fluoro-benzyl ester as colourless powder. 1H-NMR(CDCl3): 1.46 s, 9H; 3.35–3.55 m, 8H; 5.21 s, 2H; 7.02–7.20 m, 2H and 7.27–7.45 m, 2H. MS (EI): 338.1 M+.

Workup

  1. customcarbon dioxide gas bubbled into the stirred solution at rt for 1 h
  2. customwas evaporated
  3. addition150 ml of water added
  4. extractionextracted with AcOEt
  5. washThe organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. customevaporated
  8. customPurification by flash chromatography on silica gel with hexane/AcOEt 50:50

Sources & evidence

ORD record
ord-f9f5b951ab224b49a5f9e261ed3ffcd8
Source dataset
uspto-grants-2006_04
Patent number
US07022707B2

Reaction notes

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