Water → methyl 1-(3-chloropyridin-2-yl)-3-{1-hydroxy-2-[5-(trifluoromethyl)-2H-tetrazol-2-yl]ethyl}-1H-pyrazole-5-carboxylate

HRID 1630675Notes

Reaction equation

HRID 1630675 reaction equation
[H-].[Na+].[F:3][C:4]([F:11])([F:10])[C:5]1[N:6]=[N:7][NH:8][N:9]=1.[Cl:12][C:13]1[C:14]([N:19]2[C:23]([C:24]([O:26][CH3:27])=[O:25])=[CH:22][C:21]([CH:28]3[CH2:30][O:29]3)=[N:20]2)=[N:15][CH:16]=[CH:17][CH:18]=1.O>O1CCCC1.C(O)(=O)C>[Cl:12][C:13]1[C:14]([N:19]2[C:23]([C:24]([O:26][CH3:27])=[O:25])=[CH:22][C:21]([CH:28]([OH:29])[CH2:30][N:7]3[N:8]=[N:9][C:5]([C:4]([F:11])([F:10])[F:3])=[N:6]3)=[N:20]2)=[N:15][CH:16]=[CH:17][CH:18]=1

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 4217082H-Tetrazole, 5-(trifluoromethyl)-, sodium salt (1:1)HCID 86661393methyl 1-(3-chloropyridin-2-yl)-3-(oxiran-2-yl)-1H-pyrazole-5-carboxylate

Product 1

HCID 66587513methyl 1-(3-chloropyridin-2-yl)-3-{1-hydroxy-2-[5-(trifluoromethyl)-2H-tetrazol-2-yl]ethyl}-1H-pyrazole-5-carboxylateYield 80%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

51.5 mg (2.14 mmol) of sodium hydride were initially charged in 15 ml of tetrahydrofuran, and a solution of 1380 mg (2.32 mmol) of a 25% strength solution of 5-(trifluoromethyl)-2H-tetrazole in tetrahydrofuran was added at 0° C. After 20 minutes of stirring at 0° C., 500 mg (1.78 mmol) of methyl 1-(3-chloropyridin-2-yl)-3-(oxiran-2-yl)-1H-pyrazole-5-carboxylate were added, and the mixture was stirred at reflux temperature for 20 hours. The reaction mixture was poured into water, acidified with glacial acetic acid and then extracted repeatedly with ethyl acetate. The combined organic phases were washed with water and then dried over magnesium sulphate. The solvent was distilled off under reduced pressure and the residue was chromatographed on silica gel, which gave 286 mg (80% of theory) 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. (logP: 2.64/2.68; MH+: 418.0; 1H-NMR (400 MHz, CD3CN, δ, ppm): 3.73 (s, 3H), 4.31 (m, 2H), 4.48 (m, 1H), 7.10 (m, 1H), 7.54 (m, 1H), 8.05 (m, 1H), 8.50 (m, 1H).)

Workup

  1. stirringthe mixture was stirred
  2. temperatureat reflux temperature for 20 hours
  3. extractionextracted repeatedly with ethyl acetate
  4. washThe combined organic phases were washed with water
  5. dry with materialdried over magnesium sulphate
  6. distillationThe solvent was distilled off under reduced pressure
  7. customthe residue was chromatographed on silica gel, which

Sources & evidence

ORD record
ord-8d464e599bd54244a4e09e49cc7d16cb
Source dataset
uspto-grants-2014_07
Patent number
US08791139B2

Reaction notes

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