Hydrochloric Acid → 2-Chloro-4,5-difluoro-3-methylbenzonitrile
Reaction equation
N([O-])=O.[Na+].S(=O)(=O)(O)O.N[C:11]1[C:18]([CH3:19])=[C:17]([F:20])[C:16]([F:21])=[CH:15][C:12]=1[C:13]#[N:14].C(OCC)(=O)C.[ClH:28]>C(O)(=O)C>[Cl:28][C:11]1[C:18]([CH3:19])=[C:17]([F:20])[C:16]([F:21])=[CH:15][C:12]=1[C:13]#[N:14]Participants
Conditions
- Temperature
- 70 °C
Procedure
Sodium nitrite (5.6 g) is added to conc. sulfuric acid (59 ml) at below 70° C. The mixture is heated at 70° C. for 10 minutes and then cooled, and thereto is added dropwise a solution of 2-amino-4,5-difluoro-3-methylbenzonitrile (12.3 g) in acetic acid (123 ml) at below 40° C. The mixture is stirred at the same temperature for 30 minutes and then added in portions to a solution of cuprous chloride (20 g) in conc. hydrochloric acid (200 ml), and thereafter is heated at 80° C. for 30 minutes. After cooling, to the reaction mixture is added ice water, and ethyl acetate is distilled off. The resulting residue is purified by silica gel column chromatography (solvent, dichloromethane:n-hexane =1:1) to give 2-chloro-4,5-difluoro-3-methylbenzonitrile (8.0 g), as a white crystal, m.p. 59°-61° C.
Workup
- temperaturecooled
- temperatureis heated at 80° C. for 30 minutes
- temperatureAfter cooling, to the reaction mixture
- distillationis distilled off
- customThe resulting residue is purified by silica gel column chromatography (solvent, dichloromethane:n-hexane =1:1)
Sources & evidence
- ORD record
- ord-cac884d0815c4852a017dfdc36e42f73
- Source dataset
- uspto-grants-1989_10
- Patent number
- US04874764
Reaction notes
Loading…