Indazolinone → 1-[4-(5-Fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethylpentyl]-1,2-dihydroindazol-3-one

HRID 2106005Notes

Reaction equation

HRID 2106005 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:19][CH3:20])=[C:6]([C:8]([CH3:18])([CH3:17])[CH2:9][C:10]2([C:13]([F:16])([F:15])[F:14])[CH2:12][O:11]2)[CH:7]=1.[NH:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23](=[O:30])[NH:22]1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>CS(C)=O.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:19][CH3:20])=[C:6]([C:8]([CH3:18])([CH3:17])[CH2:9][C:10]([OH:11])([C:13]([F:16])([F:15])[F:14])[CH2:12][N:21]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:23](=[O:30])[NH:22]2)[CH:7]=1

Participants

6

Reactant 3

HCID 81829IndazolinoneHCID 2724254Sodium bis(trimethylsilyl)amideHCID 160992392-[2-(5-Fluoro-2-methoxyphenyl)-2-methylpropyl]-2-trifluoromethyloxirane

Product 1

HCID 104325821-[4-(5-Fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethylpentyl]-1,2-dihydroindazol-3-oneYield 21.5%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-[2-(5-fluoro-2-methoxyphenyl)-2-methylpropyl]-2-trifluoromethyloxirane (0.29 g) and 1,2-dihydroindazol-3-one (0.17 g) in anhydrous dimethylsulfoxide (1 mL) was added sodium bis(trimethylsilyl)amide (1.0M in tetrahydrofuran, 1.0 mL). After 14 days, the reaction mixture was diluted with ethyl acetate and washed twice with water. The organic phase was dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by preparative TLC (eluted with 1% ethanol-methylene chloride) to give 1-[4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethylpentyl]-1,2-dihydroindazol-3-one as a white solid (91 mg), m.p. 141° C.-144° C.

Workup

  1. washwashed twice with water
  2. dry with materialThe organic phase was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by preparative TLC (eluted with 1% ethanol-methylene chloride)

Sources & evidence

ORD record
ord-d78806e2fad649d5ab54641a52d54b00
Source dataset
uspto-grants-2009_08
Patent number
US07579469B2

Reaction notes

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