Sulfuric Acid → 1-t-butoxycarbonyl-4-[carboxy-(4-fluorophenyl)methyl]-3,6-dihydro-2H-pyridine

HRID 497336Notes

Reaction equation

HRID 497336 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH:15]([C:23]([OH:25])=[O:24])[C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)(O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].S(=O)(=O)(O)O.[OH-].[Na+].C(OC(OC(OC(C)(C)C)=O)=O)(C)(C)C.S([O-])(O)(=O)=O.[K+]>C(Cl)(Cl)Cl.O1CCOCC1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH:10]=[C:11]([CH:15]([C:23]([OH:25])=[O:24])[C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 5

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 90495Di-tert-butyl dicarbonateHCID 516920Potassium bisulfateHCID 223186301-t-Butoxycarbonyl-4-[carboxy-(4-fluorophenyl)methyl]-4-hydroxypiperidine

Product 1

HCID 223186591-t-butoxycarbonyl-4-[carboxy-(4-fluorophenyl)methyl]-3,6-dihydro-2H-pyridineYield 94.8%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 312751,4-DioxaneSolvent

Procedure

20.0 g of 1-t-Butoxycarbonyl-4-[carboxy-(4-fluorophenyl)methyl]-4-hydroxypiperidine was suspended in 40 ml of chloroform, and 40 ml of conc. sulfuric acid was added dropwise with ice-cooling. The reaction solution was refluxed with heating for 3 hours and, after ice-cooling, 250 ml of 4M sodium hydroxide solution, 200 ml of 1,4-dioxane and 14.8 g of di-t-butyldicarbonate were added. After stirring at room temperature for 30 minutes, the reaction solution was made acidic with potassium hydrogensulfate, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous sodium chloride solution and dried over anhydrous sodium sulfate. After removal of the drying agent by filtration, the filtrate was concentrated under reduced pressure. The residue was purified by a silica gel column chromatography (Wako-gel C-200, chloroform:methanol=10:1) to give 18.0 g of 1-t-butoxycarbonyl-4-[carboxy-(4-fluorophenyl)methyl]-3,6-dihydro-2H-pyridine as an oil.

Workup

  1. temperaturecooling
  2. temperatureThe reaction solution was refluxed
  3. temperaturewith heating for 3 hours
  4. temperatureafter ice-cooling
  5. extractionfollowed by extraction with chloroform
  6. washThe organic layer was washed with a saturated aqueous sodium chloride solution
  7. dry with materialdried over anhydrous sodium sulfate
  8. customAfter removal of the drying agent
  9. filtrationby filtration
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. customThe residue was purified by a silica gel column chromatography (Wako-gel C-200, chloroform:methanol=10:1)

Sources & evidence

ORD record
ord-a17445d5aa0d4d4bb8034fd3ceece422
Source dataset
uspto-grants-2005_09
Patent number
US06949552B2

Reaction notes

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