Azidotrimethylsilane → 1-(4-fluoro-2-isopropoxyphenyl)-1H-tetrazol-5(4H)-one

HRID 1754422Notes

Reaction equation

HRID 1754422 reaction equation
[Si]([N:5]=[N+:6]=[N-:7])(C)(C)C.[F:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]=[C:16]=[O:17])=[C:11]([O:18][CH:19]([CH3:21])[CH3:20])[CH:10]=1>CCOC(C)=O>[F:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]2[C:16](=[O:17])[NH:7][N:6]=[N:5]2)=[C:11]([O:18][CH:19]([CH3:21])[CH3:20])[CH:10]=1

Participants

4

Reactant 2

HCID 78378Azidotrimethylsilane2×HCID 867044744-Fluoro-1-isocyanato-2-isopropoxybenzene

Product 1

HCID 1363444061-(4-fluoro-2-isopropoxyphenyl)-1H-tetrazol-5(4H)-oneYield 81%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

This reaction with TMS-N3 was performed behind a blast shield. The crude 4-fluoro-1-isocyanato-2-isopropoxybenzene was placed under argon and trimethylsilylazide (16 mL, 118.2 mmol, 2 equiv) was added. The reaction mixture was heated to refluxed for ON under argon. After cooling to RT, the reaction mixture was concentrated under vacuum, and the residue was charged with saturated NaHCO3 (100 mL) and stirred vigorously for 5-10 min, then the basic reaction mixture was diluted with EtOAc. The layers were separated, and the organic layer was monitored by TLC to confirm that all the product had been extracted by the saturated NaHCO3 solution. EtOAc was added to the combined basic aqueous extracts, and the pH was adjusted to <3 using 6N HCl. The aqueous and organic layers were partitioned, and the aqueous layer was extracted with EtOAc 3×. The combined organic layers were dried over Na2SO4, filtered, and the solvent removed under vacuum to provide 1-(4-fluoro-2-isopropoxyphenyl)-1H-tetrazol-5(4H)-one (11.4 g, 81%) as a brown oil that was used without further purification.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto refluxed for ON under argon
  3. concentrationthe reaction mixture was concentrated under vacuum
  4. additionthe residue was charged with saturated NaHCO3 (100 mL)
  5. customthe basic reaction mixture
  6. customThe layers were separated
  7. extractionhad been extracted by the saturated NaHCO3 solution
  8. additionEtOAc was added to the combined basic aqueous extracts
  9. customThe aqueous and organic layers were partitioned
  10. extractionthe aqueous layer was extracted with EtOAc 3×
  11. dry with materialThe combined organic layers were dried over Na2SO4
  12. filtrationfiltered
  13. customthe solvent removed under vacuum

Sources & evidence

ORD record
ord-88ca5a16de9243268298d1345fed3643
Source dataset
uspto-grants-2015_10
Patent number
US09169249B2

Reaction notes

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