Cornforth reagent → [(S)-4-Benzyloxycarbonyl-1-tert-butoxycarbonyl-piperazin-2-yl]-acetic acid

HRID 1963067Notes

Reaction equation

HRID 1963067 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[CH2:24][CH2:25][OH:26])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=[O:28].[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1>C(Cl)Cl.[Cl-].[Na+].O>[CH2:17]([O:16][C:14]([N:11]1[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[C@@H:9]([CH2:24][C:25]([OH:28])=[O:26])[CH2:10]1)=[O:15])[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

5

Reactant 2

HCID 2724130Cornforth reagentHCID 68205819(S)-2-(2-Hydroxy-ethyl)-piperazine-1,4-dicarboxylic acid 4-benzyl ester 1-tert-butyl ester

Product 1

HCID 68205818[(S)-4-Benzyloxycarbonyl-1-tert-butoxycarbonyl-piperazin-2-yl]-acetic acidYield 74.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

(S)-2-(2-Hydroxy-ethyl)-piperazine-1,4-dicarboxylic acid 4-benzyl ester 1-tert-butyl ester (cf. WO 96/31501; S. Fustero et al., Org. Lett. 9 (2007), 5283; 2.862 g, 7.85 mmol) was dissolved in 78.5 ml of DCM and pyridinium dichromate (14.772 g, 39.27 mmol) was added. The mixture was stirred at room temperature overnight, then diluted into brine (330 ml) and extracted three times with EA (70 ml). The combined organic phases were washed with water (300 ml), filtered over diatomaceous earth, dried over sodium sulfate, filtered and evaporated to dryness under reduced pressure. The product was dissolved in EA and extracted three times with a 1 N solution of sodium hydroxide. The combined aqueous phases were acidified to pH 1 with 6 N hydrochloric acid, extracted with EA and the combined extracts were washed with water and brine, dried over sodium sulfate, filtered and evaporated to dryness. 2.226 g of the title compound were obtained as a thick colorless oil.

Workup

  1. extractionextracted three times with EA (70 ml)
  2. washThe combined organic phases were washed with water (300 ml)
  3. filtrationfiltered over diatomaceous earth
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated to dryness under reduced pressure
  7. dissolutionThe product was dissolved in EA
  8. extractionextracted three times with a 1 N solution of sodium hydroxide
  9. extractionextracted with EA
  10. washthe combined extracts were washed with water and brine
  11. dry with materialdried over sodium sulfate
  12. filtrationfiltered
  13. customevaporated to dryness

Sources & evidence

ORD record
ord-3ca8ff02171d46f5b1da326048603521
Source dataset
uspto-grants-2013_04
Patent number
US08415336B2

Reaction notes

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