Isoamyl Nitrite → 1-Bromo-3,5-difluoro-2-methylsulfanylbenzene

HRID 1513933Notes

Reaction equation

HRID 1513933 reaction equation
[Br:1][C:2]1[CH:8]=[C:7]([F:9])[CH:6]=[C:5]([F:10])[C:3]=1N.N(OCCC(C)C)=O.[CH3:19][S:20]SC>>[Br:1][C:2]1[CH:8]=[C:7]([F:9])[CH:6]=[C:5]([F:10])[C:3]=1[S:20][CH3:19]

Participants

4

Reactant 3

HCID 8053Isoamyl NitriteHCID 12232Dimethyl DisulfideHCID 1362852-Bromo-4,6-Difluoroaniline

Product 1

HCID 670051631-Bromo-3,5-difluoro-2-methylsulfanylbenzeneYield 66%

Conditions

Temperature
75 °C

Procedure

Dissolve 2-bromo-4,6-difluoroaniline (40 g, 192 mmol) in methyldisulfide (250 mL) and heat to 75° C. under nitrogen. Add isoamyl nitrite (67 mL, 500 mmol) dropwise via an addition funnel trough a reflux condenser (˜1 drop/sec). Large exotherm may occur if addition is too fast. After addition is complete, heat the reaction to 95° C. for 1 hour and cool to room temperature and concentrate in vacuo. Purify dark brown residue via silica gel chromatography eluting with hexanes to yield 30.3 g of 1-bromo-3,5-difluoro-2-methylsulfanyl-benzene (66%).

Workup

  1. additionLarge exotherm may occur if addition
  2. additionAfter addition
  3. temperatureheat
  4. customthe reaction to 95° C. for 1 hour
  5. temperaturecool to room temperature
  6. concentrationconcentrate in vacuo
  7. customPurify dark brown residue via silica gel chromatography
  8. washeluting with hexanes

Sources & evidence

ORD record
ord-1d3c8e07462a449f8a423a3ae6e77778
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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