Hydrochloric Acid → N-isobutyloxycarbonyl-N-{3-isobutyl-4-[1-methoxy-2,2,2-trifluoro-1-(trifluoromethyl)ethyl]phenyl}-1,3,5-trimethylpyrazole-4-carboxamide

HRID 1952267Notes

Reaction equation

HRID 1952267 reaction equation
[H-].[Na+].[CH2:3]([C:7]1[CH:8]=[C:9]([NH:24][C:25]([C:27]2[C:28]([CH3:34])=[N:29][N:30]([CH3:33])[C:31]=2[CH3:32])=[O:26])[CH:10]=[CH:11][C:12]=1[C:13]([O:22][CH3:23])([C:18]([F:21])([F:20])[F:19])[C:14]([F:17])([F:16])[F:15])[CH:4]([CH3:6])[CH3:5].[C:35](Cl)(=[O:41])[O:36][CH2:37][CH:38]([CH3:40])[CH3:39].Cl>O1CCCC1>[CH2:37]([O:36][C:35]([N:24]([C:9]1[CH:10]=[CH:11][C:12]([C:13]([O:22][CH3:23])([C:14]([F:17])([F:15])[F:16])[C:18]([F:20])([F:21])[F:19])=[C:7]([CH2:3][CH:4]([CH3:6])[CH3:5])[CH:8]=1)[C:25]([C:27]1[C:28]([CH3:34])=[N:29][N:30]([CH3:33])[C:31]=1[CH3:32])=[O:26])=[O:41])[CH:38]([CH3:40])[CH3:39]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 62365Isobutyl chloroformateHCID 86629858N-Des(isobutyraldehyde) Pyflubumide

Product 1

HCID 86629860N-isobutyloxycarbonyl-N-{3-isobutyl-4-[1-methoxy-2,2,2-trifluoro-1-(trifluoromethyl)ethyl]phenyl}-1,3,5-trimethylpyrazole-4-carboxamideYield 103.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Sodium hydride (29 mg, 60%, 0.73 mmol) was suspended in tetrahydrofuran (10 ml), and a solution of N-{3-isobutyl-4-[1-methoxy-2,2,2-trifluoro-1-(trifluoromethyl)ethyl]phenyl}-1,3,5-trimethylpyrazole-4-carboxamide (260 mg, 0.48 mmol) in tetrahydrofuran (5 ml) was added dropwise. After stirring at room temperature for 30 min, a solution of isobutyl chlorocarbonate (100 mg, 0.73 mmol) in tetrahydrofuran (2 ml) was added, and the mixture was stirred for one day. The reaction mixture was poured into diluted hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with water, dried over magnesium sulfate and concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1) to give the desired compound (280 mg).

Workup

  1. stirringthe mixture was stirred for one day
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with water
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customthe obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-edb8d6da8066408fad69cca68cac75cb
Source dataset
uspto-grants-2013_03
Patent number
US08404861B2

Reaction notes

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