Hydrochloric Acid → 1-(3-chloropyridin-2-yl)-3-{1-hydroxy-2-[5-(trifluoromethyl)-2H-tetrazol-2-yl]ethyl}-1H-pyrazole-5-carboxylic acid

HRID 1630678Notes

Reaction equation

HRID 1630678 reaction equation
[Cl:1][C:2]1[C:3]([N:8]2[C:12]([C:13]([O:15]C)=[O:14])=[CH:11][C:10]([CH:17]([OH:28])[CH2:18][N:19]3[N:23]=[N:22][C:21]([C:24]([F:27])([F:26])[F:25])=[N:20]3)=[N:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.ClC1C(N2C(C(OC)=O)=CC(C(O)CN3C(C(F)(F)F)=NN=N3)=N2)=NC=CC=1.[OH-].[Na+].Cl>C(O)C.O>[Cl:1][C:2]1[C:3]([N:8]2[C:12]([C:13]([OH:15])=[O:14])=[CH:11][C:10]([CH:17]([OH:28])[CH2:18][N:19]3[N:23]=[N:22][C:21]([C:24]([F:25])([F:27])[F:26])=[N:20]3)=[N:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 66587513methyl 1-(3-chloropyridin-2-yl)-3-{1-hydroxy-2-[5-(trifluoromethyl)-2H-tetrazol-2-yl]ethyl}-1H-pyrazole-5-carboxylateHCID 66587622methyl 1-(3-chloropyridin-2-yl)-3-{1-hydroxy-2-[5-(trifluoromethyl)-1H-tetrazol-1-yl]ethyl}-1H-pyrazole-5-carboxylate

Product 1

HCID 666599011-(3-chloropyridin-2-yl)-3-{1-hydroxy-2-[5-(trifluoromethyl)-2H-tetrazol-2-yl]ethyl}-1H-pyrazole-5-carboxylic acidYield 59.2%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

72.5 mg (0.18 mmol) of methyl 1-(3-chloropyridin-2-yl)-3-{1-hydroxy-2-[5-(trifluoromethyl)-2H-tetrazol-2-yl]ethyl}-1H-pyrazole-5-carboxylate and methyl 1-(3-chloropyridin-2-yl)-3-{1-hydroxy-2-[5-(trifluoromethyl)-1H-tetrazol-1-yl]ethyl}-1H-pyrazole-5-carboxylate in a ratio of 66:34 were dissolved in 5.0 ml of ethanol, and 21.0 mg (0.23 mmol) of 45% strength aqueous sodium hydroxide solution were added. After 1 hour of stirring at room temperature, the mixture was diluted with water and acidified with dilute hydrochloric acid. The aqueous phase was extracted repeatedly with ethyl acetate and dried over magnesium sulphate. The solvent was distilled off under reduced pressure, which gave 43 mg (48% of theory) of 1-(3-chloropyridin-2-yl)-3-{1-hydroxy-2-[5-(trifluoromethyl)-2H-tetrazol-2-yl]ethyl}-1H-pyrazole-5-carboxylic acid and 1-(3-chloropyridin-2-yl)-3-{1-hydroxy-2-[5-(trifluoromethyl)-1H-tetrazol-1-yl]ethyl}-1H-pyrazole-5-carboxylic acid in a ratio of 73:27. (logP: 1.68/1.37; MH+: 404.0/404.0

Workup

  1. extractionThe aqueous phase was extracted repeatedly with ethyl acetate
  2. dry with materialdried over magnesium sulphate
  3. distillationThe solvent was distilled off under reduced pressure, which

Sources & evidence

ORD record
ord-333cfb7d79c346b5aa3a21a1154ced3b
Source dataset
uspto-grants-2014_07
Patent number
US08791139B2

Reaction notes

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