Methyl iodide → (S)-2-(4-Methoxybutyl)-piperazine-1,4-dicarboxylic acid di-tert-butyl ester

HRID 131413Notes

Reaction equation

HRID 131413 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][C@@H:9]1[CH2:21][CH2:22][CH2:23][CH2:24][OH:25])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:26]I.[H-].[Na+]>CN(C=O)C.[Cl-].[Na+].O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:18])([CH3:19])[CH3:20])=[O:15])[CH2:10][C@@H:9]1[CH2:21][CH2:22][CH2:23][CH2:24][O:25][CH3:26])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 58626015(S)-2-(4-Hydroxybutyl)-piperazine-1,4-dicarboxylic acid di-tert-butyl ester

Product 1

HCID 58625892(S)-2-(4-Methoxybutyl)-piperazine-1,4-dicarboxylic acid di-tert-butyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

Into a room temperature, stirred solution of (S)-2-(4-hydroxybutyl)-piperazine-1,4-dicarboxylic acid di-tert-butyl ester (0.344 g, 0.95 mmol), and MeI (0.179 mL, 2.87 mmol) in DMF (5 mL) add NaH (0.042 g, 1.05 mmol, 20% in mineral oil). Stir overnight. Dilute the mixture with 75% brine (50 mL) and extract with EtOAc (3×100 mL). Concentrate the organic layers under reduced pressure, dilute with EtOAc (40 mL) and wash with 75% brine (5×25 mL). Dry the organic layer over Na2SO4, and filter. Concentrate the mixture under reduced pressure and purify by silica gel chromatography eluting with 20% to 98% EtOAc in hexanes. Combine the purified fractions, concentrate under reduced pressure and place under vacuum to give the title compound: yellow tar (0.209 g), mass spectrum (m/e):373.13 (M+H).

Workup

  1. extractionextract with EtOAc (3×100 mL)
  2. concentrationConcentrate the organic layers under reduced pressure
  3. additiondilute with EtOAc (40 mL)
  4. washwash with 75% brine (5×25 mL)
  5. dry with materialDry the organic layer over Na2SO4
  6. filtrationfilter
  7. concentrationConcentrate the mixture under reduced pressure
  8. custompurify by silica gel chromatography
  9. washeluting with 20% to 98% EtOAc in hexanes
  10. concentrationCombine the purified fractions, concentrate under reduced pressure and place under vacuum

Sources & evidence

ORD record
ord-3100839f177f4d36b9bfa53d183028c7
Source dataset
uspto-grants-2008_06
Patent number
US07384934B2

Reaction notes

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