Ethyl orthoformate → HCID 131734296, compound

HRID 1502145Notes

Reaction equation

HRID 1502145 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([CH2:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH:5]=[CH:4][N:3]=1.C(OCC)(OCC)OCC.[N-:26]=[N+:27]=[N-:28].[Na+].[C:30](=O)(O)[O-].[Na+]>C(O)(=O)C.O>[C:12]([O:11][C:9](=[O:10])[CH2:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([N:1]2[CH:30]=[N:28][N:27]=[N:26]2)[CH:7]=1)([CH3:15])([CH3:14])[CH3:13]

Participants

7

Reactant 4

HCID 31214Ethyl orthoformateHCID 33557Sodium AzideHCID 516892Sodium BicarbonateHCID 91619103HCID 91619103, compound

Product 1

HCID 131734296HCID 131734296, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of tert-butyl (2-aminopyridin-4-yl)acetate (18 mg, 0.087 mmol) in glacial acetic acid (1 mL) was added triethyl orthoformate (43 μL, 0.261 mmol) and sodium azide (17 mg, 0.261 mmol). The reaction mixture was heated at 80° C. for 3 hours in a sealed vial and then cooled to ambient temperature. Once cooled, water (1.5 mL) and solid sodium bicarbonate were added until a pH range of 6-7 was achieved. The aqueous layer was extracted with ethyl acetate (3×6 mL). The combined organic layers were then dried over sodium sulfate, filtered and concentrated in vacuo. The crude residue was purified via reverse phase reverse-phase HPLC (TMC Pro-Pac C18; 10-100% 0.1% trifluoroacetic acid in acetonitrile/0.1% trifluoroacetic acid in water gradient) to afford tert-butyl[2-(1H-tetrazol-1-yl)pyridin-4-yl]acetate: LC-MS: (M+H-28)+234.

Workup

  1. temperaturethen cooled to ambient temperature
  2. temperatureOnce cooled
  3. extractionThe aqueous layer was extracted with ethyl acetate (3×6 mL)
  4. dry with materialThe combined organic layers were then dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude residue was purified via reverse phase reverse-phase HPLC (TMC Pro-Pac C18; 10-100% 0.1% trifluoroacetic acid in acetonitrile/0.1% trifluoroacetic acid in water gradient)

Sources & evidence

ORD record
ord-28bf96faa9ef44e3b6783f3cdea59c5f
Source dataset
uspto-grants-2015_12
Patent number
US09206199B2

Reaction notes

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