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

HRID 2173324Notes

Reaction equation

HRID 2173324 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>[N:1]1([C:2]2[CH:3]=[CH:4][C:5]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[N:6][CH:7]=2)[CH:14]=[N:26][N:25]=[N:24]1

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 column chromatography via silica gel to give ethyl [5-(1H-tetrazol-1-yl)pyridin-2-yl]acetate. 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 column chromatography via silica gel

Sources & evidence

ORD record
ord-a2effec9765642769bead6eb9b145ac3
Source dataset
uspto-grants-2015_06
Patent number
US09056859B2

Reaction notes

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