4-Piperidinecarboxylic acid → 1-{[(9H-Fluoren-9-yl)methoxy]carbonyl}piperidine-4-carboxylic acid

HRID 482562Notes

Reaction equation

HRID 482562 reaction equation
[NH:1]1[CH2:9][CH2:8][CH:4]([C:5]([OH:7])=[O:6])[CH2:3][CH2:2]1.C(=O)([O-])ON1C(=O)CC([CH2:18][CH:19]2[C:31]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[C:25]3[C:20]2=[CH:21][CH:22]=[CH:23][CH:24]=3)C1=O.[C:35](=O)([O-:37])[O-:36].[Na+].[Na+].O1CCOCC1>>[C:35]([N:1]1[CH2:9][CH2:8][CH:4]([C:5]([OH:7])=[O:6])[CH2:3][CH2:2]1)([O:37][CH2:18][CH:19]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[C:25]2[C:20]1=[CH:21][CH:22]=[CH:23][CH:24]=2)=[O:36]

Participants

4

Reactant 3

HCID 37734-Piperidinecarboxylic acidHCID 67151127Sodium carbonate dioxaneHCID 71304114(9H-fluoren-9-yl)methyl-2,5-dioxopyrrolidin-1-yl carbonate

Product 1

HCID 27364901-{[(9H-Fluoren-9-yl)methoxy]carbonyl}piperidine-4-carboxylic acidYield 95%

Procedure

To a solution of 10.0 g (77.4 mmol) of isonipecotic acid (Aldrich) in 1N sodium carbonate/dioxane (1:1) at 0° C., was added 21.1 g (77.4 mmol) of 9-fluorenylmethylsuccinimidyl carbonate, portionwise. After 14 h, the dioxane was removed in vacuo, and the suspension diluted with 1200 mL of water. After extraction with 2 portions of ether (discarded), the aqueous solution was cooled in an ice bath and acidified to pH 3 with concentrated hydrochloric acid. The slurry was extracted twice with ethyl acetate and the combined organics washed with water, brine, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated to 500 mL, diluted with 700 mL of hexane, and placed in a refrigerator overnight. The product was collected on a filter and dried in vacuo to give 25.8 g (95%) of N-FMOC-isonipecotic acid as a colorless solid.

Workup

  1. customthe dioxane was removed in vacuo
  2. additionthe suspension diluted with 1200 mL of water
  3. extractionAfter extraction with 2 portions of ether (discarded)
  4. temperaturethe aqueous solution was cooled in an ice bath
  5. extractionThe slurry was extracted twice with ethyl acetate
  6. washthe combined organics washed with water, brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated to 500 mL
  10. additiondiluted with 700 mL of hexane
  11. customplaced in a refrigerator overnight
  12. customThe product was collected on
  13. filtrationa filter
  14. customdried in vacuo

Sources & evidence

ORD record
ord-8dc084a657f044c5a9baea114759abde
Source dataset
uspto-grants-1998_08
Patent number
US05798337

Reaction notes

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