Sodium methanethiolate → 2-Chloro-3-fluoro-5-methylthiomethylpyridine

HRID 1924848Notes

Reaction equation

HRID 1924848 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([CH2:9]Br)=[CH:4][N:3]=1.[CH3:11][S-:12].[Na+]>C(O)C>[Cl:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([CH2:9][S:12][CH3:11])=[CH:4][N:3]=1

Participants

4

Reactant 2

HCID 4378561Sodium methanethiolateHCID 592970785-(Bromomethyl)-2-chloro-3-fluoropyridine

Product 1

HCID 592970862-Chloro-3-fluoro-5-methylthiomethylpyridineYield 65%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 2-chloro-3-fluoro-5-bromomethylpyridine (3.7 g, 16.5 mmol) in ethanol (40 mL) was treated with sodium thiomethoxide solid (2.31 g, 33 mmol) portionwise at 0° C. After the addition was over, the mixture was stirred at room temperature overnight. Most of the solvent ethanol was removed under reduced pressure and the residue was re-taken into dichloromethane. Brine solution was added and two phases mixed and separated. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated. The resulting residue was purified on silica gel using 8% EtOAc in hexane as eluent to give 2.04 g of the desired 2-chloro-3-fluoro-5-methylthiomethylpyridine in 65% yield. GC-MS calcd. for C7H7ClFNS: 191.66. Found: 191.

Workup

  1. additionAfter the addition
  2. customMost of the solvent ethanol was removed under reduced pressure
  3. additionBrine solution was added
  4. additiontwo phases mixed
  5. customseparated
  6. dry with materialThe organic layer was dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resulting residue was purified on silica gel using 8% EtOAc in hexane as eluent

Sources & evidence

ORD record
ord-f18df472a383467fa91b29527a2b8a5a
Source dataset
uspto-grants-2012_05
Patent number
US08178565B2

Reaction notes

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