Sulfuric Acid → ethyl 5-[3-(trifluoromethoxy)phenoxy]-2-[4-(trifluoromethyl)phenyl]-2H-1,2,3-triazole-4-carboxylate

HRID 623702Notes

Reaction equation

HRID 623702 reaction equation
N[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[N:12]1[N:16]=[C:15]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:14]([O:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([O:29][C:30]([F:33])([F:32])[F:31])[CH:24]=2)=[N:13]1.S(=O)(=O)(O)O.N(OCCC(C)C)=O.OP=O>C(O)C.[Cl-].[Na+]>[F:33][C:30]([F:31])([F:32])[O:29][C:25]1[CH:24]=[C:23]([CH:28]=[CH:27][CH:26]=1)[O:22][C:14]1[C:15]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[N:16][N:12]([C:3]2[CH:4]=[CH:5][C:6]([C:8]([F:11])([F:10])[F:9])=[CH:7][CH:2]=2)[N:13]=1

Participants

7

Reactant 4

HCID 1118Sulfuric AcidHCID 8053Isoamyl NitriteHCID 22497phosphenous acidHCID 901093272-(2-amino-4-trifluoromethyl-phenyl)-5-(3-trifluoromethoxy-phenoxy)-2H-[1,2,3]triazole-4-carboxylic acid ethyl ester2×

Product 1

HCID 90111572ethyl 5-[3-(trifluoromethoxy)phenoxy]-2-[4-(trifluoromethyl)phenyl]-2H-1,2,3-triazole-4-carboxylate

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 5234Sodium ChlorideSolvent

Conditions

Temperature
-20 °C

Procedure

To a solution of ethyl 2-[2-amino-4-(trifluoromethyl)phenyl]-5-[3-(trifluoromethoxy)phenoxy]-2H-1,2,3-triazole-4-carboxylate (i.e. the product of Step G, 0.70 g, 1.5 mmol) in ethanol (20 mL) was added concentrated sulfuric acid (2 mL). The stirring mixture was cooled to −20° C., and then isopentyl nitrite (0.91 g, 8.8 mmol) was added dropwise over 5 min. The reaction mixture was stirred at −20° C. for 1 h, after which an aqueous solution of hypophosphorus acid (3.9 g, 29.4 mmol, 50% in water) was added. The solution was stirred at 23° C. for 14 h. The reaction mixture was diluted with saturated aqueous sodium chloride solution (20 mL), extracted with ethyl acetate (2×40 mL), and washed with saturated aqueous sodium bicarbonate solution (2×20 mL). The organic layer was dried (MgSO4) and concentrated under reduced pressure to afford the crude residue which was purified by chromatography on silica gel eluting with 0 to 15% ethyl acetate in hexanes to obtain the title compound (0.55 g) as a colorless solid.

Workup

  1. stirringThe solution was stirred at 23° C. for 14 h
  2. extractionextracted with ethyl acetate (2×40 mL)
  3. washwashed with saturated aqueous sodium bicarbonate solution (2×20 mL)
  4. dry with materialThe organic layer was dried (MgSO4)
  5. concentrationconcentrated under reduced pressure
  6. customto afford the crude residue which
  7. customwas purified by chromatography on silica gel eluting with 0 to 15% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-5b62db37eb7347bca56db35ce47c3e77
Source dataset
uspto-grants-2016_04
Patent number
US09302999B2

Reaction notes

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