Toluene → HCID 26316549, compound

HRID 1809154Notes

Reaction equation

HRID 1809154 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][CH:12]=1)[O:5][CH2:6][C:7]([OH:9])=[O:8].C1(C)C=CC=CC=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH:32]([NH:34][NH:35][CH:36]=O)=O>CN(C=O)C>[N:34]1[N:35]=[CH:36][N:1]([C:2]2[CH:3]=[C:4]([CH:10]=[CH:11][CH:12]=2)[O:5][CH2:6][C:7]([OH:9])=[O:8])[CH:32]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 123421,2-HydrazinedicarboxaldehydeHCID 235515(3-Aminophenoxy)acetic acidHCID 521998p-Toluenesulfonic acid monohydrate

Product 1

HCID 26316549HCID 26316549, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a round bottom flask was added (3-amino-phenoxy)-acetic acid 2 (167 mg, 1.0 mmol, 1.0 eq.), toluene (5.0 mL), DMF (0.5 mL), p-toluene sulfonic acid monohydrate (209 mg, 1.1 mmol, 1.1 eq.), and sym-diformyl hydrazine (96.8 mg, 1.1 mmol, 1.1 eq.). The mixture was refluxed overnight. Upon cooling to RT, the reaction mixture separated out into two layers with product in the bottom brown oil layer and toluene in the clear top layer. The toluene layer was removed; water was added to the brown oil and then extracted with EtOAc 3×. The combined organic layers were then dried with Na2SO4, concentrated via rotary evaporation, and then triturated with ether to give (3-[1,2,4]Triazol-4-yl-phenoxy)-acetic acid 24 as an orange solid (65.0 mg, 30% yield). LC/MSD (HP Series 1100 MSD) MS (ES+) m/z 220.1 (M+H)+1 1H-NMR, Varian 400 MHz (DMSO-d6) δ 9.10 (s, 2H), 7.48 (m, 1H), 7.39 (t, 1H), 7.31 (dd, 1H), 7.00 (dd, 1H), 4.80 (s, 2H) ppm.

Workup

  1. temperatureThe mixture was refluxed overnight
  2. customthe reaction mixture separated out into two layers with product in the bottom brown oil layer and toluene in the clear top layer
  3. customThe toluene layer was removed
  4. additionwater was added to the brown oil
  5. extractionextracted with EtOAc 3×
  6. dry with materialThe combined organic layers were then dried with Na2SO4
  7. concentrationconcentrated via rotary evaporation
  8. customtriturated with ether

Sources & evidence

ORD record
ord-77e4bfc1268f46f3a05305dafd0c6e46
Source dataset
uspto-grants-2013_01
Patent number
US08362017B2

Reaction notes

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