Pyrazole → 1-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-1H-pyrazole-4-carboxylic acid methyl ester

HRID 1505286Notes

Reaction equation

HRID 1505286 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[N:7][NH:8][CH:9]=1)=[O:4].[H-].[Na+].Cl[C:13]1[CH2:17][C:16]([C:22]2[CH:27]=[C:26]([Cl:28])[CH:25]=[C:24]([Cl:29])[CH:23]=2)([C:18]([F:21])([F:20])[F:19])[O:15][N:14]=1.N1C=CC=N1>C(#N)C>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[N:7][N:8]([C:13]2[CH2:17][C:16]([C:22]3[CH:27]=[C:26]([Cl:28])[CH:25]=[C:24]([Cl:29])[CH:23]=3)([C:18]([F:19])([F:20])[F:21])[O:15][N:14]=2)[CH:9]=1)=[O:4]

Participants

6

Reactant 4

HCID 1048PyrazoleHCID 24758Sodium hydrideHCID 9793760Methyl 1H-pyrazole-4-carboxylateHCID 584979653-Chloro-5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazole

Product 1

HCID 584979541-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-1H-pyrazole-4-carboxylic acid methyl esterYield 100.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

To a solution of pyrazole-4-carboxylic acid methyl ester (756 mg) in acetonitrile (30 ml) under argon was added sodium hydride (240 mg). The reaction mixture was stirred at room temperature for 1 h. 15 mf of this solution was added dropwise to a solution of chloroisoxazoline of example 17.2 (630 mg) in acetonitrile (10 ml). It was then stirred at room temperature for 1 h; 15 ml of pyrazole solution was added again and the mixture was stirred over the weekend. The reaction was quenched by adding water and dichloromethane. The two layers were separated. The aqueous layer was extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated. The crude residue was purified by column chromatography (from c-Hex (100%) to c-Hex:EtOAc (80:20)) to afford the title intermediate (810 mg) as a yellow solid. 1H-NMR (CDCl3, 400 MHz): 8.60 (s, 1H), 8.10 (s, 1H), 7.5 (m, 2H), 7.45 (m, 1H), 4.35 (d, 1H), 4.00 (d, 1H), 3.75 (s, 3H).

Workup

  1. stirringIt was then stirred at room temperature for 1 h
  2. stirringthe mixture was stirred over the weekend
  3. customThe reaction was quenched
  4. additionby adding water and dichloromethane
  5. customThe two layers were separated
  6. extractionThe aqueous layer was extracted with dichloromethane
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated
  10. customThe crude residue was purified by column chromatography (from c-Hex (100%) to c-Hex:EtOAc (80:20))

Sources & evidence

ORD record
ord-3050d64d93234c30b462df3515abc61f
Source dataset
uspto-grants-2015_12
Patent number
US09216973B2

Reaction notes

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