Acetic Anhydride → 2-Chloro-6-fluoro-3-methylbenzonitrile

HRID 374955Notes

Reaction equation

HRID 374955 reaction equation
Cl.[NH2:2]O.[F:4][C:5]1[CH:12]=[CH:11][C:10]([CH3:13])=[C:9]([Cl:14])[C:6]=1[CH:7]=O.C(OC(=O)C)(=O)C>N1C=CC=CC=1>[F:4][C:5]1[CH:12]=[CH:11][C:10]([CH3:13])=[C:9]([Cl:14])[C:6]=1[C:7]#[N:2]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 443297Hydroxyamine hydrochlorideHCID 7363342-Chloro-6-fluoro-3-methylbenzaldehyde

Product 1

HCID 177506682-Chloro-6-fluoro-3-methylbenzonitrile

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Hydroxylamine hydrochloride (1.1 parts) is added to a solution of 2-fluoro-5-methyl-6-chlorobenzaldehyde in pyridine, and the mixture is stirred for 15 minutes at room temperature. Acetic anhydride (1.3 parts) is then added and the mixture stirred at ambient temperature overnight to effect complete dehydration of the oxime to the nitrile. Most of the pyridine is removed by concentration under vacuum, then the residue is partitioned between ether and water. The organic phase is washed with brine, dried (MgSO4), filtered through silica gel, concentrated, then triturated in hexane to afford 2-fluoro-5-methyl-6-chlorobenzonitrile as light yellow crystals.

Workup

  1. stirringthe mixture stirred at ambient temperature overnight
  2. customMost of the pyridine is removed by concentration under vacuum
  3. customthe residue is partitioned between ether and water
  4. washThe organic phase is washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered through silica gel
  7. concentrationconcentrated
  8. customtriturated in hexane

Sources & evidence

ORD record
ord-9bced95ab4ed484ca81c9597ff729689
Source dataset
uspto-grants-1996_01
Patent number
US05482974

Reaction notes

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