Hydrochloric Acid → 2-Amino-6-difluoromethoxy-benzonitrile

HRID 39221

Reaction equation

HRID 39221 reaction equation
[F:1][CH:2]([F:15])[O:3][C:4]1[CH:11]=[CH:10][CH:9]=[C:8]([N+:12]([O-])=O)[C:5]=1[C:6]#[N:7].[Sn](Cl)Cl.Cl.[OH-].[Na+]>C(O)(C)C.O>[NH2:12][C:8]1[CH:9]=[CH:10][CH:11]=[C:4]([O:3][CH:2]([F:1])[F:15])[C:5]=1[C:6]#[N:7]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 24479Stannous ChlorideHCID 581007642-Difluoromethoxy-6-nitrobenzonitrile

Product 1

HCID 581007652-Amino-6-difluoromethoxy-benzonitrileYield 121%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent

Procedure

To a solution of 2-difluoromethoxy-6-nitro-benzonitrile (4.0 g, 14.9 mmol) (Example I3) in isopropanol (100 ml) is added tin(II) chloride (10.2 g, 53.6 mmol). Aqueous hydrochloric acid (concentrated) (14.4 ml) is added slowly and the reaction mixture is heated to reflux for 30 minutes. The reaction mixture is cooled to room temperature, diluted with water and the pH is adjusted to 10 by addition of NaOH (2M). The mixture is extracted three times with ethyl acetate. The combined organic phases are dried over sodium sulfate and concentrated to yield 2-amino-6-difluoromethoxy-benzonitrile (3.32 g, 93% yield) in pure form. 1H-NMR (CDCl3, 400 MHz): 7.05 (t, 1H), 6.65 (d, 1H), 6.55 (t, 1H), 6.50 (t, 1H), 4.25 (s, br, 2H) ppm.

Workup

  1. temperaturethe reaction mixture is heated
  2. temperatureto reflux for 30 minutes
  3. extractionThe mixture is extracted three times with ethyl acetate
  4. dry with materialThe combined organic phases are dried over sodium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-17568dea09934574afe97a0723533b5e
Source dataset
uspto-grants-2013_09
Patent number
US08524896B2

Linked notes

Loading…