Sodium bis(trimethylsilyl)amide → 1-[2-difluoromethyl-4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methylpentyl]-1H-quinolin-4-one

HRID 2106057Notes

Reaction equation

HRID 2106057 reaction equation
[OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1.[F:12][C:13]1[CH:14]=[CH:15][C:16]([O:29][CH3:30])=[C:17]([C:19]([CH3:28])([CH3:27])[CH2:20][C:21]2([CH:24]([F:26])[F:25])[CH2:23][O:22]2)[CH:18]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>CS(C)=O.C(OCC)(=O)C>[F:26][CH:24]([F:25])[C:21]([OH:22])([CH2:20][C:19]([C:17]1[CH:18]=[C:13]([F:12])[CH:14]=[CH:15][C:16]=1[O:29][CH3:30])([CH3:28])[CH3:27])[CH2:23][N:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:2](=[O:1])[CH:3]=[CH:4]1

Participants

6

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 578097912-[2-(5-Fluoro-2-methoxyphenyl)-2-methylpropyl]-2-difluoromethyloxiraneHCID 178516385quinolin-4-ol

Product 1

HCID 100250741-[2-difluoromethyl-4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methylpentyl]-1H-quinolin-4-one

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the 4-hydroxyquinoline and 2-[2-(5-fluoro-2-methoxyphenyl)-2-methylpropyl]-2-difluoromethyloxirane in DMSO (1.0 mL) stirred under nitrogen was added NaHMDS (1.2 mL, 1.0M in THF) dropwise. The mixture was stirred at room temperature for 15 days. The mixture was diluted with ethyl acetate, washed with water, dried, filtered, and evaporated in vacuo. Trituration of the residue with diethyl ether gave the product 1-[2-difluoromethyl-4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methylpentyl]-1H-quinolin-4-one as a crystalline solid that was collected by filtration and air dried (77.7 mg, 20%).

Workup

  1. washwashed with water
  2. customdried
  3. filtrationfiltered
  4. customevaporated in vacuo

Sources & evidence

ORD record
ord-d79fe6ed1144421787b9eb634d28c900
Source dataset
uspto-grants-2009_08
Patent number
US07579469B2

Reaction notes

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