Sodium Azide → HCID 178525126, compound

HRID 2384701Notes

Reaction equation

HRID 2384701 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17]#[N:18])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N-:19]=[N+:20]=[N-:21].[Na+]>CC(O)C.O.C(OCC)(=O)C.[Br-].[Zn+2].[Br-]>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17]2[NH:21][N:20]=[N:19][N:18]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 2

HCID 33557Sodium AzideHCID 22028286Benzyl 4-cyanopiperidine-1-carboxylate

Product 1

HCID 178525126HCID 178525126, compoundYield 132.3%

Reagents, catalysts & solvents 4

HCID 10421208Zinc bromideCatalystHCID 962WaterSolventHCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 4-cyano-piperidine-1-carboxylic acid benzyl ester (0.73 g, 3.0 mmol), sodium azide (0.39 g, 6.0 mmol) and zinc bromide (0.33 g, 1.5 mmol) in 2-propanol (5 mL) and water (10 mL) was stirred at 120° C. for 3 days into a pressure tube. The reaction mixture was then partitioned between aqueous 3.0N HCl (1.5 mL) and ethyl acetate and then stirred vigorously until 2 clear phases were obtained. Aqueous layer was then extracted with ethyl acetate and combined ethyl acetate layers dried over Na2SO4, filtered, and the solvent evaporated in vacuo to yield a crude residue. The residue was dissolved in ethyl acetate (10 mL) and washed with 0.25N aqueous sodium hydroxide. Aqueous layer was acidified to pH=1 with aqueous 3.0N HCl and extracted with ethyl acetate. Ethyl acetate layer was dried over Na2SO4, filtered, and the solvent evaporated in vacuo to yield a crude gum. The gum was purified via flash chromatography (4% methanol in dichloromethane) to yield 4-(1H-Tetrazol-5-yl)-piperidine-1-carboxylic acid benzyl ester as a gum (1.14 g, 66%).

Workup

  1. customThe reaction mixture was then partitioned between aqueous 3.0N HCl (1.5 mL) and ethyl acetate
  2. stirringstirred vigorously until 2 clear phases
  3. customwere obtained
  4. extractionAqueous layer was then extracted with ethyl acetate and combined ethyl acetate layers
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customthe solvent evaporated in vacuo
  8. customto yield a crude residue
  9. washwashed with 0.25N aqueous sodium hydroxide
  10. extractionextracted with ethyl acetate
  11. dry with materialEthyl acetate layer was dried over Na2SO4
  12. filtrationfiltered
  13. customthe solvent evaporated in vacuo
  14. customto yield a crude gum
  15. customThe gum was purified via flash chromatography (4% methanol in dichloromethane)

Sources & evidence

ORD record
ord-84cfb601f05848bfb8a43539c44c0fba
Source dataset
uspto-grants-2012_09
Patent number
US08263781B2

Reaction notes

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