Triethylamine → Di-tert-butyl 2-(hydroxymethyl)piperazine-1,4-dicarboxylate

HRID 1792005Notes

Reaction equation

HRID 1792005 reaction equation
C(N(CC)CC)C.ClC(OCC(C)C)=O.[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH:24]1[C:36](O)=[O:37])=[O:22])([CH3:19])([CH3:18])[CH3:17]>O1CCCC1>[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH:24]1[CH2:36][OH:37])=[O:22])([CH3:19])([CH3:18])[CH3:17]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 112559791,4-Di-Boc-piperazine-2-carboxylic acid

Product 1

HCID 22711445Di-tert-butyl 2-(hydroxymethyl)piperazine-1,4-dicarboxylateYield 68.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (6.06 g) and isobutyl chloroformate (7.51 g) were added to a solution of piperazine-1,2,4-tricarboxylic acid 1,4-di-tert-butyl ester (16.52 g) in tetrahydrofuran (200 ml) at −10° C., and the mixture was stirred for 3 hours. The reaction solution was filtered, and treated with 20 ml aqueous solution of sodium borohydride (7.72 g) at −10° C. After the mixture was stirred for 1 hour, ethyl acetate (500 ml) and water (200 ml) were added thereto, and excessive sodium borohydride was quenched with 1 N hydrochloric acid. The organic layer was washed with water (200 ml), followed by saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate. Then, the solvent was removed by distillation at reduced pressure. The residue was purified by silica gel column chromatography to obtain 10.87 g of the title compound from a fraction eluted with hexane-ethyl acetate (1:1).

Workup

  1. filtrationThe reaction solution was filtered
  2. additiontreated with 20 ml aqueous solution of sodium borohydride (7.72 g) at −10° C
  3. stirringAfter the mixture was stirred for 1 hour
  4. additionethyl acetate (500 ml) and water (200 ml) were added
  5. customexcessive sodium borohydride was quenched with 1 N hydrochloric acid
  6. washThe organic layer was washed with water (200 ml)
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customThen, the solvent was removed by distillation at reduced pressure
  9. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-f0e7e5f9437c441f8924ef16ae231e4b
Source dataset
uspto-grants-2006_07
Patent number
US07074798B2

Reaction notes

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