Pyridine → Tert-butyl 4-cyanopiperidine-1-carboxylate

HRID 1670754Notes

Reaction equation

HRID 1670754 reaction equation
[NH:1]1[CH2:9][CH2:8][CH:4]([C:5]([NH2:7])=O)[CH2:3][CH2:2]1.N1[CH:15]=[CH:14][CH:13]=CC=1.FC(F)(F)[C:18]([O:20]C(=O)C(F)(F)F)=[O:19].[C:29](=O)([O-])O.[Na+]>C(Cl)Cl>[C:14]([O:20][C:18]([N:1]1[CH2:9][CH2:8][CH:4]([C:5]#[N:7])[CH2:3][CH2:2]1)=[O:19])([CH3:13])([CH3:15])[CH3:29]

Participants

6

Reactant 4

HCID 1049PyridineHCID 37724-PiperidinecarboxamideHCID 9845Trifluoroacetic anhydrideHCID 516892Sodium Bicarbonate

Product 1

HCID 1514443Tert-butyl 4-cyanopiperidine-1-carboxylateYield 88%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Isonipecotic acid amide (Tokyo Chemical Industry CO., LTD., 2.1 g) was dissolved in methylene chloride (50 ml). The mixture was cooled to 0° C., pyridine (4 ml) and trifluoroacetic acid anhydride (5.6 ml) were added, and the mixture was stirred for 8 hr. After completion of the reaction, a saturated aqueous sodium hydrogencarbonate solution was added, and the mixture was extracted with methylene chloride. The organic layer was washed with water, and dried. The solvent was evaporated under reduced pressure. The obtained residue was dissolved in diethyl ether (34 ml) and cooled to 0° C. A 2N aqueous sodium hydroxide solution (34 ml) was added di-tert-Butyl bicarbonate (7.2 g) dissolved in diethyl ether (10 ml) was added, and the mixture was stirred at room temperature for 12 hr. After completion of the reaction, the reaction mixture was partitioned by adding water. The organic layer was washed with water, and dried. The solvent was evaporated under reduced pressure to give 4-cyanopiperidine-1-carboxylic acid tert-butyl ester (3.1 g, yield 88%).

Workup

  1. customAfter completion of the reaction
  2. extractionthe mixture was extracted with methylene chloride
  3. washThe organic layer was washed with water
  4. customdried
  5. customThe solvent was evaporated under reduced pressure
  6. dissolutionThe obtained residue was dissolved in diethyl ether (34 ml)
  7. temperaturecooled to 0° C
  8. additionA 2N aqueous sodium hydroxide solution (34 ml) was added di-tert-Butyl bicarbonate (7.2 g)
  9. dissolutiondissolved in diethyl ether (10 ml)
  10. additionwas added
  11. stirringthe mixture was stirred at room temperature for 12 hr
  12. customAfter completion of the reaction
  13. customthe reaction mixture was partitioned
  14. additionby adding water
  15. washThe organic layer was washed with water
  16. customdried
  17. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-ba68063fc8604da38dedb5a0e2446275
Source dataset
uspto-grants-2011_08
Patent number
US07994196B2

Reaction notes

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