Methanol → 4-Amino-5-fluoro-2-methoxybenzonitrile

HRID 630409Notes

Reaction equation

HRID 630409 reaction equation
[CH3:1][OH:2].[NH2:3][C:4]1[C:11]([F:12])=[CH:10][C:7]([C:8]#[N:9])=[C:6](F)[CH:5]=1>O1CCCC1>[NH2:3][C:4]1[C:11]([F:12])=[CH:10][C:7]([C:8]#[N:9])=[C:6]([O:2][CH3:1])[CH:5]=1

Participants

4

Reactant 2

HCID 887MethanolHCID 27359004-Amino-2,5-difluorobenzonitrile

Product 1

HCID 185196344-Amino-5-fluoro-2-methoxybenzonitrileYield 97%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixture of methanol (10.48 mL, 0.25 mol) and anh. tetrahydrofuran (60 mL) was added dropwise a solution of potassium tert-butilate (6.76 g, 0.05 mol) in anh. tetrahydrofuran (52 mL) at 0° C. under nitrogen atmosphere. The mixture was stirred for minutes at room temperature and then 4-amino-2,5-difluorobenzonitrile (4 g, 0.02 mol) was added. The reaction mixture was stirred at 70° C. for 3 hours. The solvent was partially removed and ether was added into the mixture. The organic layer was washed with bicarbonate and brine, dried and filtered. The organic solvent was removed under reduced pressure to give the title compound as a yellow solid (97%), which was used in the next step without further purification.

Workup

  1. stirringThe reaction mixture was stirred at 70° C. for 3 hours
  2. customThe solvent was partially removed
  3. additionether was added into the mixture
  4. washThe organic layer was washed with bicarbonate and brine
  5. customdried
  6. filtrationfiltered
  7. customThe organic solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-8242f9408a2247d490ba5d83aed76b62
Source dataset
uspto-grants-2016_04
Patent number
US09315463B2

Reaction notes

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