Dimethyl Disulfide → 4-Fluoro-2-methylsulfanyl-benzoic acid

HRID 1179304Notes

Reaction equation

HRID 1179304 reaction equation
Br[C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].Cl[Mg]C.C([Li])CCC.[CH3:20][S:21]SC>C1COCC1>[F:11][C:9]1[CH:8]=[CH:7][C:3]([C:4]([OH:6])=[O:5])=[C:2]([S:21][CH3:20])[CH:10]=1

Participants

6

Reactant 4

HCID 12232Dimethyl DisulfideHCID 12681692-Bromo-4-fluorobenzoic acidHCID 178418332HCID 178418332, compoundHCID 178418339Butyllithium

Product 1

HCID 162280324-Fluoro-2-methylsulfanyl-benzoic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of 2-bromo-4-fluorobenzoic acid (15 g, 68.5 mmol, Marshallton Research Laboratories) in THF (150 mL) under argon at 0° C. was treated with chloro(methyl)magnesium (5.64 g, 75.34 mmol, 2.94 M in THF) over 5 minutes. The temperature during addition was maintained below 10° C. The resulting solution was cooled to −78° C. and n-butyllithium (9.65 g, 150.7 mmol, 2.5M in hexanes) was added over 10 minutes. The reaction was kept below −65° C. during the addition. The reaction was stirred at −78° C. for 50 minutes. A solution of (methyldithio)methane (38.71 g, 410.9 mmol) in THF (20 mL), precooled to −78° C., was added by cannula. The reaction was stirred for 10 minutes, warmed to zero ° C. and stirred at zero ° C. for 2 hours until a solid began to precipitate. The reaction was allowed to warm to 25° C. and stirred overnight. The reaction was poured into 1N HCl and extracted with EtOAc. The water layer was extracted with EtOAc twice more, the organic layers were combined, dried over Na2SO4, filtered and evaporated. The crude solid was suspended in 5% EtOAc/Hexanes and stirred for an hour, then filtered and dried to give the product as a white solid.

Workup

  1. additionThe temperature during addition
  2. temperaturewas maintained below 10° C
  3. additionThe reaction was kept below −65° C. during the addition
  4. customprecooled to −78° C.
  5. additionwas added by cannula
  6. stirringThe reaction was stirred for 10 minutes
  7. temperaturewarmed to zero ° C.
  8. stirringstirred at zero ° C. for 2 hours until a solid
  9. customto precipitate
  10. temperatureto warm to 25° C.
  11. stirringstirred overnight
  12. additionThe reaction was poured into 1N HCl
  13. extractionextracted with EtOAc
  14. extractionThe water layer was extracted with EtOAc twice more
  15. dry with materialdried over Na2SO4
  16. filtrationfiltered
  17. customevaporated
  18. stirringstirred for an hour
  19. filtrationfiltered
  20. customdried

Sources & evidence

ORD record
ord-0d78e96069fc4fd6b3ce61963c562c9d
Source dataset
uspto-grants-2007_10
Patent number
US07279487B2

Reaction notes

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