Sodium Azide → 1-(2-Fluoro-3-methoxyphenyl)-5-methoxy-1H-1,2,3-triazole-4-carboxylic acid

HRID 1508332Notes

Reaction equation

HRID 1508332 reaction equation
Cl[C:2]1[C:3]([F:18])=[C:4]([N:8]2[C:12]([O:13][CH3:14])=[C:11]([C:15]([OH:17])=[O:16])[N:10]=[N:9]2)[CH:5]=[CH:6][CH:7]=1.FC1[C:26]([O:27]C)=CC=CC=1N.N([O-])=O.[Na+].[N-]=[N+]=[N-].[Na+]>C(O)(C(F)(F)F)=O.O>[F:18][C:3]1[C:2]([O:27][CH3:26])=[CH:7][CH:6]=[CH:5][C:4]=1[N:8]1[C:12]([O:13][CH3:14])=[C:11]([C:15]([OH:17])=[O:16])[N:10]=[N:9]1

Participants

7

Reactant 4

HCID 33557Sodium AzideHCID 225046662-Fluoro-3-methoxyanilineHCID 23668193Sodium NitriteHCID 712556781-(3-Chloro-2-fluorophenyl)-5-methoxy-1H-1,2,3-triazole-4-carboxylic acid

Product 1

HCID 712557051-(2-Fluoro-3-methoxyphenyl)-5-methoxy-1H-1,2,3-triazole-4-carboxylic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
0 °C

Procedure

1-(3-Chloro-2-fluorophenyl)-5-methoxy-1H-1,2,3-triazole-4-carboxylic acid: To a solution of 2-fluoro-3-methoxyaniline (1 g, 7.09 mmol) in TFA (10 mL) and water (5 mL) at 0° C. was added an aq. solution of NaNO2 (0.733 g, 10.63 mmol) dropwise. The resulting mixture was stirred at 0° C. for 0.5 h and NaN3 (0.921 g, 14.17 mmol) was added portionwise. The reaction mixture was gradually warmed to rt and stirred for 4 h. The reaction was quenched with water (150 mL) and extracted with EtOAc (2×100 mL). The organic layer was washed with sodium phosphate solution (10%) and brine (50 mL), dried, and concentrated. The resulting brown oil was re-dissolved in DMSO (20 mL) and added t-butylpropiolate (1 mL) followed by K2CO3 (1 g), Cu(OAc)2 (0.2 g), and sodium ascorbate (100 mg). The resulting mixture was stirred at rt overnight. The reaction was quenched with water (200 mL) and extracted with EtOAc (2×100 mL). The organic layer was dried and concentrated. The residue was purified by silica gel chromatography to yield the desired product as brown oil. 1H NMR (400 MHz, CDCl3) δ 13.19 (br. s., 1H), 7.36-7.20 (m, 2H), 7.17-6.95 (m, 1H), 6.76 (td, J=8.1, 1.3 Hz, 1H), 3.91 (s, 3H), 1.74-1.49 (m, 10H). MS(ESI) m/z: 238.0 (M+H)+.

Workup

  1. temperatureThe reaction mixture was gradually warmed to rt
  2. stirringstirred for 4 h
  3. customThe reaction was quenched with water (150 mL)
  4. extractionextracted with EtOAc (2×100 mL)
  5. washThe organic layer was washed with sodium phosphate solution (10%) and brine (50 mL)
  6. customdried
  7. concentrationconcentrated
  8. dissolutionThe resulting brown oil was re-dissolved in DMSO (20 mL)
  9. additionadded t-butylpropiolate (1 mL)
  10. stirringThe resulting mixture was stirred at rt overnight
  11. customThe reaction was quenched with water (200 mL)
  12. extractionextracted with EtOAc (2×100 mL)
  13. customThe organic layer was dried
  14. concentrationconcentrated
  15. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-c06f17e0e26b4022b7e7093ed7e7db6d
Source dataset
uspto-grants-2015_12
Patent number
US09221818B2

Reaction notes

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