Triethylamine → tert-Butyl (2R)-2-[(4-benzylpiperazin-1-yl)carbonyl]piperazine-1-carboxylate

HRID 2371153Notes

Reaction equation

HRID 2371153 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:14]([N:21]1[CH2:26][CH2:25][NH:24][CH2:23][C@@H:22]1[C:27](O)=[O:28])([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15].C(N(CC)CC)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([C:27]([C@H:22]2[CH2:23][NH:24][CH2:25][CH2:26][N:21]2[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[O:28])[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 759941-BenzylpiperazineHCID 2724699PyBOPHCID 24820285(2R)-1-(tert-Butoxycarbonyl)piperazine-2-carboxylic acid

Product 1

HCID 57656790tert-Butyl (2R)-2-[(4-benzylpiperazin-1-yl)carbonyl]piperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

1-Benzylpiperazine (2.7 ml) and (2R)-1-BOC-piperazine-2-carboxylic acid (3.571 g) were suspended in DMF (150 ml) and stirred at 0° C. Triethylamine (4.33 ml) was added followed by PyBOP reagent (8.08 g). The mixture was allowed to warm to room temperature overnight, concentrated to approximately a third of the volume in vacuo and partitioned between brine (75 ml) and ethyl acetate (2×200 ml). Combined organic extracts were treated with saturated aqueous sodium bicarbonate (75 ml) and brine (75 ml), dried (sodium sulphate), concentrated in vacuo using high vacuum to remove DMF traces and purified by chromatography eluting with 0-15% methanol/dichloromethane. This gave tert-butyl (2R)-2-[(4-benzylpiperazin-1-yl)carbonyl]piperazine-1-carboxylate as a white glass (5.01 g).

Workup

  1. temperatureto warm to room temperature overnight
  2. concentrationconcentrated to approximately a third of the volume in vacuo
  3. custompartitioned between brine (75 ml) and ethyl acetate (2×200 ml)
  4. additionCombined organic extracts were treated with saturated aqueous sodium bicarbonate (75 ml) and brine (75 ml)
  5. dry with materialdried (sodium sulphate)
  6. concentrationconcentrated in vacuo
  7. customto remove DMF traces
  8. custompurified by chromatography
  9. washeluting with 0-15% methanol/dichloromethane

Sources & evidence

ORD record
ord-d90f1f5f2d524d9b9f6a792823c5ee5f
Source dataset
uspto-grants-2014_04
Patent number
US08710224B2

Reaction notes

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