Ethyl orthoformate → ethyl [5-(1H-tetrazol-1-yl)pyridin-2-yl]acetate

HRID 1502109Notes

Reaction equation

HRID 1502109 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[N:6][CH:7]=1.[CH:14](OCC)(OCC)OCC.[N-:24]=[N+:25]=[N-:26].[Na+]>CC(O)=O>[CH2:12]([O:11][C:9](=[O:10])[CH2:8][C:5]1[CH:4]=[CH:3][C:2]([N:1]2[CH:14]=[N:26][N:25]=[N:24]2)=[CH:7][N:6]=1)[CH3:13]

Participants

5

Reactant 3

HCID 31214Ethyl orthoformateHCID 33557Sodium AzideHCID 21876034Ethyl 2-(5-aminopyridin-2-yl)acetate

Product 1

HCID 67518188ethyl [5-(1H-tetrazol-1-yl)pyridin-2-yl]acetate

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of ethyl (5-aminopyridin-2-yl)acetate (1.0 g, 5.5 mmol), CH(OEt)3 (1.31 g, 8.80 mmol) in AcOH (10 mL) was added NaN3 (0.54 g, 8.3 mmol) at room temperature. The mixture was heated to 80° C. and stirred for 3 hours. The mixture was concentrated under reduce pressure. Water was added, and the mixture was extracted with EtOAc. The combined organic layer was washed with brine, dried over anhydrous Na2SO4, concentrated and the residue was purified by silica column chromatography to give title compound: 1H-NMR (400 MHz, CDCl3) δ 9.03 (s, 1H), 8.90 (s, 1H), 8.06 (d, J=8.4 Hz, 1H), 7.58 (d, J=8.4 Hz, 1H), 4.21 (q, J=7.2 Hz, 2H), 3.96 (s, 2H), 1.29 (t, J=7.2 Hz, 3H).

Workup

  1. concentrationThe mixture was concentrated
  2. additionWater was added
  3. extractionthe mixture was extracted with EtOAc
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated
  7. customthe residue was purified by silica column chromatography

Sources & evidence

ORD record
ord-5857efa6597c4a488e32aaca3caaf5c4
Source dataset
uspto-grants-2015_12
Patent number
US09206199B2

Reaction notes

Loading…