Potassium Phosphate, Tribasic → ethyl [6-(1H-tetrazol-1-yl)pyridin-3-yl]acetate

HRID 2173316Notes

Reaction equation

HRID 2173316 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:4][CH:3]=1.F[C:15](F)(F)C(O[Si](C)(C)C)=O.[Si]([N:29]=[N+:30]=[N-:31])(C)(C)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CCOC(C)=O>[N:1]1([C:2]2[N:7]=[CH:6][C:5]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:4][CH:3]=2)[CH:15]=[N:29][N:30]=[N:31]1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 67863Acetic acid, 2,2,2-trifluoro-, trimethylsilyl ester2×HCID 78378AzidotrimethylsilaneHCID 67143734Ethyl 2-(6-aminopyridin-3-yl)acetate

Product 1

HCID 77230693ethyl [6-(1H-tetrazol-1-yl)pyridin-3-yl]acetate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

A 1 L 3-neck flask was purged with nitrogen and charged with a solution of ethyl (6-aminopyridin-3-yl)acetate (31.7 g, 176 mmol) in EtOAc (317 mL) at +22° C. Then 30 mL of TMS trifluoroacetate was added (1.0 equiv) while cooling in a water bath. A mild exotherm to +25° C. and partial crystallization was observed. After 5 min, triethylorthoformate was added (44.0 mL, 264 mmol) followed by TMS-azide (28.0 mL, 211 mmol). The resulting suspension was stirred at +23° C. After 15 min, an additional 10 mL of TMS trifluoroacetate was added (0.30 equiv). A clear soln formed after ˜10 min. The mixture was stirred for 3 days at +20° C. whereupon a thin, light yellow suspension had formed. The mixture was cooled in an ice bath, and 200 mL of 1M aq K3PO4 was added while maintaining the temperature below +20° C. Then 465 mL EtOAc was added to solubilize the product. The layers were separated (pH of aq˜8), then the organic phase was washed with 2×250 mL water, and concentrated to a thick slurry. Then 400 mL of n-heptane was added to the concentrated organic phase over 20 min. After 30 rnM, the suspension was filtered to afford the title tetrazole product.

Workup

  1. customA 1 L 3-neck flask was purged with nitrogen
  2. temperaturewhile cooling in a water bath
  3. customA mild exotherm to +25° C. and partial crystallization
  4. additiontriethylorthoformate was added (44.0 mL, 264 mmol)
  5. waitAfter 15 min
  6. customA clear soln formed after ˜10 min
  7. stirringThe mixture was stirred for 3 days at +20° C. whereupon a thin, light yellow suspension
  8. customhad formed
  9. temperatureThe mixture was cooled in an ice bath
  10. temperaturewhile maintaining the temperature below +20° C
  11. customThe layers were separated (pH of aq˜8)
  12. washthe organic phase was washed with 2×250 mL water
  13. concentrationconcentrated to a thick slurry
  14. additionThen 400 mL of n-heptane was added to the concentrated organic phase over 20 min
  15. filtrationAfter 30 rnM, the suspension was filtered

Sources & evidence

ORD record
ord-3d827c49ac0c44b0a75b865f26881390
Source dataset
uspto-grants-2015_06
Patent number
US09056859B2

Reaction notes

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