Hydrochloric Acid → (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid

HRID 1486965Notes

Reaction equation

HRID 1486965 reaction equation
[F:1][C:2]([F:27])([F:26])[C:3]1[CH:4]=[C:5]([C:13]2[N:17]=[CH:16][N:15](/[CH:18]=[CH:19]\[C:20]([O:22]C(C)C)=[O:21])[N:14]=2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[Li+].[OH-].Cl>C1COCC1.O>[F:27][C:2]([F:1])([F:26])[C:3]1[CH:4]=[C:5]([C:13]2[N:17]=[CH:16][N:15](/[CH:18]=[CH:19]\[C:20]([OH:22])=[O:21])[N:14]=2)[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 53386343(Z)-isopropyl 3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylate

Product 1

HCID 86703006(Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acidYield 94.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

A 3-neck round-bottom flask was charged with a solution of (Z)-isopropyl 3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylate (3) (130 g, 1.0 eq.) in THF (1.3 L) and treated with a solution of LiOH (69.3 g, 5 eq) in water (1.3 L). The reaction mixture was stirred at ambient temperature for 3-4 h before being diluted with 400 mL water, acidified (pH=2-3) with dilute aqueous HCl and extracted with EtOAc (3×1 L). The combined organic layers were washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford 110 g (94% yield) of desired compound (4); Z/E ratio=90.0/8.2 by LCMS.

Workup

  1. extractionextracted with EtOAc (3×1 L)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-6d0817bb96b54895b98415d5fc356a4e
Source dataset
uspto-grants-2016_08
Patent number
US09428490B2

Reaction notes

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