Sodium Chloride → 1,1,1-Trifluoro-4-(3-fluoro-2-methoxyphenyl)-4-methyl-2-[(5-methyl-1H-indazol-4-ylimino)-methyl]-pentan-2-ol

HRID 1869405Notes

Reaction equation

HRID 1869405 reaction equation
[F:1][C:2]1[C:3]([O:20][CH3:21])=[C:4]([C:8]([CH3:19])([CH3:18])[CH2:9][C:10]([OH:17])([C:13]([F:16])([F:15])[F:14])[CH:11]=O)[CH:5]=[CH:6][CH:7]=1.[CH3:22][C:23]1[C:24]([NH2:32])=[C:25]2[C:29](=[CH:30][CH:31]=1)[NH:28][N:27]=[CH:26]2.C1(C)C(C)=CC=CC=1.[Cl-].[Na+]>C(OCC)(=O)C>[F:16][C:13]([F:14])([F:15])[C:10]([CH:11]=[N:32][C:24]1[C:23]([CH3:22])=[CH:31][CH:30]=[C:29]2[C:25]=1[CH:26]=[N:27][NH:28]2)([OH:17])[CH2:9][C:8]([C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[O:20][CH3:21])([CH3:19])[CH3:18]

Participants

6

Reactant 4

HCID 5234Sodium ChlorideHCID 7237O-XyleneHCID 179890864-(3-Fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentanalHCID 193544325-Methyl-1H-indazol-4-amine

Product 1

HCID 686820761,1,1-Trifluoro-4-(3-fluoro-2-methoxyphenyl)-4-methyl-2-[(5-methyl-1H-indazol-4-ylimino)-methyl]-pentan-2-olYield 79%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

4-(3-Fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)-pentanal (308 mg, 1.0 mmol) and 5-methyl-1H-indazol-4-ylamine (148 mg, 1.0 mmol) are introduced into 15.0 ml of xylene and mixed with titanium(IV)ethylate (0.42 ml, 2.0 mmol). After 3 hours under reflux, the reaction mixture is allowed to cool to room temperature. After ethyl acetate and saturated sodium chloride solution are added, it is stirred vigorously for 30 minutes at room temperature. The deposited precipitate is suctioned off, the aqueous phase is separated, and the organic phase is dried on sodium sulfate. The purification is carried out by means of chromatography on silica gel with hexane/ethyl acetate (30-40% ethyl acetate). 345 mg (79% of theory) of 1,1,1-trifluoro-4-(3-fluoro-2-methoxyphenyl)-4-methyl-2-[(5-methyl-1H-indazol-4-ylimino)methyl]-pentan-2-ol is obtained.

Workup

  1. temperatureAfter 3 hours under reflux
  2. customthe aqueous phase is separated
  3. customthe organic phase is dried on sodium sulfate
  4. customThe purification

Sources & evidence

ORD record
ord-6e78970c57c541e6b62ded19af05e5fc
Source dataset
uspto-grants-2009_12
Patent number
US07638515B2

Reaction notes

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