Methyl iodide → 1-(4-fluoro-2-isopropoxyphenyl)-4-methyl-1H-tetrazol-5(4H)-one

HRID 1754423Notes

Reaction equation

HRID 1754423 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12](=[O:13])[NH:11][N:10]=[N:9]2)=[C:4]([O:14][CH:15]([CH3:17])[CH3:16])[CH:3]=1.[C:18]([O-])([O-])=O.[K+].[K+].IC>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12](=[O:13])[N:11]([CH3:18])[N:10]=[N:9]2)=[C:4]([O:14][CH:15]([CH3:17])[CH3:16])[CH:3]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 1363444061-(4-fluoro-2-isopropoxyphenyl)-1H-tetrazol-5(4H)-one

Product 1

HCID 867044751-(4-fluoro-2-isopropoxyphenyl)-4-methyl-1H-tetrazol-5(4H)-oneYield 81%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 1-(4-fluoro-2-isopropoxyphenyl)-1H-tetrazol-5(4H)-one (4.10 g, 17.2 mmol, 1 equiv), K2CO3 (7.15 g, 52.0 mmol, 3 equiv), and iodomethane (3.25 mL, 52.0 mmol, 3 equiv) in DMF (40 mL) was stirred at RT ON. The reaction mixture was partitioned between water and EtOAc, then the layers were separated. The aqueous layer was extracted with EtOAc 2×, and the combined organic layer was washed with brine 1×. The organic layer was dried over Na2SO4, filtered, and concentrated to dryness to provide 1-(4-fluoro-2-isopropoxyphenyl)-4-methyl-1H-tetrazol-5(4H)-one (3.50 g, 81%) as a brown oil that was used without further purification. 1H NMR (300 MHz; d6-DMSO) δ 7.46-7.51 (dd, 1H, J=6.3 Hz, 8.4 Hz), 7.20-7.25 (dd, 1H, J=2.7 Hz, 11 Hz), 6.87-6.94 (td, 1H, J=2.7 Hz, 8.1 Hz), 4.63-4.75 (hept, 1H, J=6.0 Hz), 3.59 (s, 3H), 1.16-1.18 (d, 6H, J=6.0 Hz); 19F NMR (282 MHz; d6-DMSO) δ −107.0 (sextet); m/z=253 (M+H)+.

Workup

  1. customThe reaction mixture was partitioned between water and EtOAc
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted with EtOAc 2×
  4. washthe combined organic layer was washed with brine 1×
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-507073bf3aed4efab16ca6c7eb9b2e35
Source dataset
uspto-grants-2015_10
Patent number
US09169249B2

Reaction notes

Loading…