Hydrochloric Acid → 4-Amino-3-chloro-2-fluoro-5-nitro-benzoic acid

HRID 2104064Notes

Reaction equation

HRID 2104064 reaction equation
[OH-].[NH4+:2].[Cl:3][C:4]1[C:5]([F:17])=[C:6]([CH:10]=[C:11]([N+:14]([O-:16])=[O:15])[C:12]=1F)[C:7]([OH:9])=[O:8].Cl>O>[NH2:2][C:12]1[C:11]([N+:14]([O-:16])=[O:15])=[CH:10][C:6]([C:7]([OH:9])=[O:8])=[C:5]([F:17])[C:4]=1[Cl:3]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14923Ammonium Hydroxide2×HCID 155499183-Chloro-2,4-difluoro-5-nitrobenzoic acid

Product 1

HCID 211141824-Amino-3-chloro-2-fluoro-5-nitro-benzoic acidYield 85.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Ammonium hydroxide solution (6.88 g, ˜30% in water, 58.9 mmol) is added to a solution of 3-chloro-2,4-difluoro-5-nitro-benzoic acid 2a (3.5 g, 14.7 mmol) in water (16 mL) at 0° C. with stirring. Upon completion of the ammonium hydroxide addition the reaction mixture is warmed to room temperature. After 5 hours the reaction mixture is cooled to 0° C. and concentrated HCl is carefully added until the pH of the reaction mixture is near zero. The solid is collected by filtration and washed with water and diethyl ether. The solids are transferred to a round bottom flask as a solution in MeOH and EtOAc and concentrated under reduced pressure to give 2.96 g of a yellow solid. The filtrate is partitioned between diethyl ether and water and the organic layer is washed with brine. The combined organic extracts are dried (Na2SO4) and concentrated under reduced pressure to give 0.65 g of product. Recovered a total of 3.61 g (104%) of pure desired product that is carried forward without further purification.

Workup

  1. temperatureAfter 5 hours the reaction mixture is cooled to 0° C.
  2. filtrationThe solid is collected by filtration
  3. washwashed with water and diethyl ether
  4. customThe solids are transferred to a round bottom flask as a solution in MeOH
  5. concentrationEtOAc and concentrated under reduced pressure

Sources & evidence

ORD record
ord-faabed412ced4816b6799fd008d900bf
Source dataset
uspto-grants-2009_08
Patent number
US07576114B2

Reaction notes

Loading…