Sodium Iodide → 5-(3,5-Difluorobenzyl)-2-fluorobenzonitrile

HRID 512942Notes

Reaction equation

HRID 512942 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:9](O)[C:10]2[CH:11]=[CH:12][C:13]([F:18])=[C:14]([CH:17]=2)[C:15]#[N:16])[CH:5]=[C:6]([F:8])[CH:7]=1.[I-].[Na+].Cl[Si](C)(C)C>C(#N)C.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[C:6]([F:8])[CH:7]=1)[CH2:9][C:10]1[CH:11]=[CH:12][C:13]([F:18])=[C:14]([CH:17]=1)[C:15]#[N:16]

Participants

6

Reactant 3

HCID 5238Sodium IodideHCID 6397ChlorotrimethylsilaneHCID 686715605-((3,5-Difluorophenyl)(hydroxy)methyl)-2-fluorobenzonitrile

Product 1

HCID 441342595-(3,5-Difluorobenzyl)-2-fluorobenzonitrileYield 94.3%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-[(3,5-Difluoro-phenyl)-hydroxy-methyl]-2-fluoro-benzonitrile (3.5 g, 13.3 mmol) and sodium iodide (20 g, 133 mmol) are stirred in acetonitrile (50 mL) under nitrogen at 60° C. To the reaction mixture is gradually added chlorotrimethylsilane (17 mL, 134 mmol) over a period of 8 hours. The mixture is diluted with ethyl acetate and washed with water, saturated aqueous sodium bicarbonate, 10% aqueous sodium thiosulfate and brine. Purification of the crude by chromatography over silica gel (EtOAc/hexane 5:100) afforded 3.1 g of the title compound (88% yield).

Workup

  1. customof 8 hours
  2. washwashed with water, saturated aqueous sodium bicarbonate, 10% aqueous sodium thiosulfate and brine
  3. customPurification of the crude by chromatography over silica gel (EtOAc/hexane 5:100)

Sources & evidence

ORD record
ord-539b4d6827c048019326648e4930cf0b
Source dataset
uspto-grants-2015_08
Patent number
US09102662B2

Reaction notes

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