Sodium hydride → 3-Oxo-4-(2-pyrrolidin-1-yl-ethyl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 559322Notes

Reaction equation

HRID 559322 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][NH:13][C:12](=[O:16])[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].Cl[CH2:18][CH2:19][N:20]1[CH2:24][CH2:23][CH2:22][CH2:21]1.Cl.ClCCN1CCCC1>CN(C)C(=O)C.C1(C)C=CC=CC=1>[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][N:13]([CH2:18][CH2:19][N:20]2[CH2:24][CH2:23][CH2:22][CH2:21]2)[C:12](=[O:16])[CH2:11]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 816681-(2-Chloroethyl)pyrrolidine hydrochlorideHCID 816691-(2-Chloroethyl)pyrrolidineHCID 3157178Tert-butyl 3-oxopiperazine-1-carboxylate

Product 1

HCID 669995983-Oxo-4-(2-pyrrolidin-1-yl-ethyl)-piperazine-1-carboxylic acid tert-butyl esterYield 42%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 31374DimethylacetamideSolvent

Procedure

Sodium hydride (55% dispersion in mineral oil, 1.96 g, 45 mmol) was added portionwise at room temperature to a solution of 3-oxo-piperazine-1-carboxylic acid tert-butyl ester (6.01 g, 30.0 mmol) in N,N-dimethylacetamide (150 ml), then a solution of 1-(2-chloroethyl)-pyrrolidine in toluene [prepared from commercially available 1-(2-chloroethyl)-pyrrolidine hydrochloride (16.1 g, 94.5 mmol) by partitioning between toluene (70 ml) and 1 M aq. sodium hydroxide solution (70 ml) and drying of the organic layer with Na2SO4] was added dropwise. The reaction mixture was stirred at room temperature for 16 h, then heated at 75° C. for 80 min. After cooling, the reaction mixture was partitioned between diethyl ether amid sat. aq. sodium hydrogencarbonate solution. The organic layer was dried (Na2SO4) and evaporated. Crystallization of the residue from diethyl ether afforded the title compound (3.74 g, 42%). White solid, MS (ISP)=298.2 (M+H)+.

Workup

  1. customby partitioning between toluene (70 ml) and 1 M aq. sodium hydroxide solution (70 ml)
  2. dry with materialdrying of the organic layer with Na2SO4]
  3. additionwas added dropwise
  4. temperatureheated at 75° C. for 80 min
  5. temperatureAfter cooling
  6. customthe reaction mixture was partitioned between diethyl ether amid sat. aq. sodium hydrogencarbonate solution
  7. dry with materialThe organic layer was dried (Na2SO4)
  8. customevaporated
  9. customCrystallization of the residue from diethyl ether

Sources & evidence

ORD record
ord-f813c9cf688047439481ad033c127251
Source dataset
uspto-grants-2011_11
Patent number
US08063042B2

Reaction notes

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