Nitric Acid → 1-(4-fluoro-2-hydroxy-5-nitrophenyl)-4-methyl-1H-tetrazol-5(4H)-one

HRID 1754424Notes

Reaction equation

HRID 1754424 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12](=[O:13])[N:11]([CH3:14])[N:10]=[N:9]2)=[C:4]([O:15]C(C)C)[CH:3]=1.[N+:19]([O-])([OH:21])=[O:20]>OS(O)(=O)=O>[F:1][C:2]1[C:7]([N+:19]([O-:21])=[O:20])=[CH:6][C:5]([N:8]2[C:12](=[O:13])[N:11]([CH3:14])[N:10]=[N:9]2)=[C:4]([OH:15])[CH:3]=1

Participants

4

Reactant 2

HCID 944Nitric AcidHCID 867044751-(4-fluoro-2-isopropoxyphenyl)-4-methyl-1H-tetrazol-5(4H)-one

Product 1

HCID 867044761-(4-fluoro-2-hydroxy-5-nitrophenyl)-4-methyl-1H-tetrazol-5(4H)-oneYield 83%

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidSolvent

Procedure

A solution of 1-(4-fluoro-2-isopropoxyphenyl)-4-methyl-1H-tetrazol-5(4H)-one (3.50 g, 13.9 mmol, 1 equiv) in H2SO4 (35 mL) was cooled in ice/water bath. To the cooled solution, was added HNO3 (fuming >90%; 715 uL, 15.3 mmol, 1.1 equiv) dropwise, and the cooled reaction mixture was allowed to warm to RT over 2 h. The reaction mixture was quenched with ice, and extracted with EtOAc 3×. The organic layer was then extracted with saturated NaHCO3 3×. The basic aqueous layer was acidified to pH <3 with 6N HCl. Then, the acidic layer was extracted with EtOAc 3×, and the organic layer was dried over Na2SO4, filtered, and concentrated to dryness to provide 1-(4-fluoro-2-hydroxy-5-nitrophenyl)-4-methyl-1H-tetrazol-5(4H)-one (2.94 g, 83%) as brown solid that was used without further purification. 1H NMR (300 MHz; d6-DMSO) δ 12.5 (bs, 1H), 8.41-8.44 (d, 1H, J=8.7 Hz), 7.04-7.08 (d, 1H, J=13 Hz), 3.59 (s, 3H); 19F NMR (282 MHz; d6-DMSO) δ −111.3 (q); m/z=256 (M+H)+.

Workup

  1. customthe cooled reaction mixture
  2. customThe reaction mixture was quenched with ice
  3. extractionextracted with EtOAc 3×
  4. extractionThe organic layer was then extracted with saturated NaHCO3 3×
  5. extractionThen, the acidic layer was extracted with EtOAc 3×
  6. dry with materialthe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-9d12eddca62a4a6482f6bba6465ebb0b
Source dataset
uspto-grants-2015_10
Patent number
US09169249B2

Reaction notes

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