Hydrochloric Acid → (S)-4-benzyl 1-tert-butyl 2-(hydroxymethyl)piperazine-1,4-dicarboxylate

HRID 1006349Notes

Reaction equation

HRID 1006349 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:15])[CH2:10][C@H:9]1[C:24](OCC)=[O:25])=[O:7])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Li+].Cl.[Cl-].[Na+]>C(OCC)(=O)C.CO>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][CH2:17][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)=[O:15])[CH2:10][C@H:9]1[CH2:24][OH:25])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 5234Sodium ChlorideHCID 4148881Lithium borohydrideHCID 59016652(S)-4-Benzyl 1-tert-butyl 2-ethyl piperazine-1,2,4-tricarboxylate

Product 1

HCID 69745232(S)-4-benzyl 1-tert-butyl 2-(hydroxymethyl)piperazine-1,4-dicarboxylateYield 100.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

Under nitrogen atmosphere, to a solution of (2S)-2-ethoxycarbonylpiperazine-1,4-dicarboxylic acid 4-benzyl ester 1-tert-butyl ester (9.35 g) was added portionwise lithium borohydride (1.82 g), and the reaction mixture was stirred for 90 minutes. After methanol (2.32 ml) was added dropwise to the solution under ice-cooling, the mixture was stirred at room temperature for 17 hours. 1N Hydrochloric acid (80 ml) was added dropwise under ice-cooling, and ethyl acetate (100 ml) and sodium chloride (6 g) was added to it. The organic layer was washed with brine, dried over magnesium sulfate, and evaporated under reduced pressure to give colorless oil. The oil was purified by column chromatography on silica gel (90 g) using a mixed solvent of hexane and ethyl acetate (3:2). The fractions containing the objective compound were collected and evaporated under reduced pressure to give (2S)-2-(hydroxymethyl)piperazine-1,4-dicarboxylic acid 4-benzyl ester 1-tert-butyl ester (8.40 g) as a colorless oil.

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred at room temperature for 17 hours
  3. temperaturecooling
  4. washThe organic layer was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. customevaporated under reduced pressure
  7. customto give colorless oil
  8. customThe oil was purified by column chromatography on silica gel (90 g)
  9. additionThe fractions containing the objective compound
  10. customwere collected
  11. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-061e190ebd084282b9261fe67d98dd1a
Source dataset
uspto-grants-2004_09
Patent number
US06787543B2

Reaction notes

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