2,3,6-Trifluorobenzonitrile → 3,6-Difluoro-2-methoxybenzonitrile

HRID 1874692Notes

Reaction equation

HRID 1874692 reaction equation
[Na].[CH3:2][O-:3].[Na+].F[C:6]1[C:13]([F:14])=[CH:12][CH:11]=[C:10]([F:15])[C:7]=1[C:8]#[N:9]>CO>[F:14][C:13]1[C:6]([O:3][CH3:2])=[C:7]([C:10]([F:15])=[CH:11][CH:12]=1)[C:8]#[N:9]

Participants

5

Reactant 3

HCID 1456222,3,6-TrifluorobenzonitrileHCID 5360545SodiumHCID 10942334Sodium Methoxide

Product 1

HCID 457907333,6-Difluoro-2-methoxybenzonitrileYield 91%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

Methanol (600 mL) was treated portionwise with sodium (Alfa, 16.1 g, 0.702 gatoms, 1.05 equiv.). The sodium methoxide solution was cooled to room temperature and added dropwise to a solution of 2,3,6-trifluorobenzonitrile (Matrix, 105 g, 0.699 mol) in methanol (600 ml) at room temperature. After addition was complete the mixture was stirred for 1 hour at room temperature before removing the methanol under reduced pressure. The residue was partitioned between diethyl ether (500 ml) and water (500 mL). The organic layer was removed, dried over MgSO4, filtered and evaporated to give the crude product. This was purified by distillation using a 6″ vigreux column @ 20 mmHg, oil bath 160° C., head temp 120° C. to give the title compound as a white solid (108 g, 91%)

Workup

  1. additionAfter addition
  2. custombefore removing the methanol under reduced pressure
  3. customThe residue was partitioned between diethyl ether (500 ml) and water (500 mL)
  4. customThe organic layer was removed
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customto give the crude product
  9. distillationThis was purified by distillation
  10. custom20 mmHg, oil bath 160° C., head temp 120° C.

Sources & evidence

ORD record
ord-6bf40cd67b404c73b16d62e5f4c7ac61
Source dataset
uspto-grants-2012_11
Patent number
US08304446B2

Reaction notes

Loading…