Ammonia → 2-Amino-5-(methanesulfonyl)benzonitrile

HRID 1846297Notes

Reaction equation

HRID 1846297 reaction equation
Cl[C:2]1[CH:8]=[C:7]([S:9]([CH3:12])(=[O:11])=[O:10])[CH:6]=[CH:5][C:3]=1[NH2:4].[Cu][C:14]#[N:15].N.O>CN1CCCC1>[NH2:4][C:3]1[CH:5]=[CH:6][C:7]([S:9]([CH3:12])(=[O:11])=[O:10])=[CH:8][C:2]=1[C:14]#[N:15]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 962WaterHCID 25801Benzenamine, 2-chloro-4-(methylsulfonyl)-HCID 178418546HCID 178418546, compound

Product 1

HCID 150200262-Amino-5-(methanesulfonyl)benzonitrile

Reagents, catalysts & solvents 1

HCID 84541-MethylpyrrolidineSolvent

Conditions

Temperature
180 °C

Procedure

To a solution of 2-chloro-4-methylsulfonyl aniline (1.0 g, 4.9 mmol) in N-methylpyrrolidine (10 mL) was added copper (I) cyanide (4.35 g, 48.6 mmol) under nitrogen. The reaction mixture was stirred at 180° C. for 72 hours, cooled to room temperature, poured to a 1:1 mixture of ammonia and water (200 mL), stirred for 1 hour, and then filtered off. The residue was washed with CH2Cl2 (50 mL) and filtrate was extracted with CH2Cl2 (3×20 mL). The combined organic layers were backwashed with water (50 mL), dried over sodium sulfate, and concentrated to provide crude material, which was purified by flash column chromatography (silica gel; 230-400 mesh; ethyl acetate/hexanes=1:5) to obtain 2-amino-5-methanesulfonyl-benzonitrile as a white solid. Yield: 0.1 g (13%). A suspension of potassium hydroxide (2.05 g, 36.7 mmol) in ethylene glycol (9 mL) was heated to 80° C. KOH was dissolved completely at this stage. 2-Amino-5-methanesulfonyl-benzonitrile (0.900 g, 4.59 mmol) was added to the reaction mixture and the bath temperature was increased to 185° C. and stirred for 16 hours. The resultant reaction mixture was cooled to room temperature, diluted with water (20 mL), and extracted with CH2Cl2 (3×30 mL). The aqueous layer was acidified with 2 N HCl to pH 4-5, extracted with EtOAc (3×30 mL), and the combined organic layers were backwashed with water (30 mL), then brine (30 mL), dried over sodium sulfate, and evaporated, to obtain 2-amino-5-methanesulfonyl-benzoic acid. Yield: 0.750 g (75%).

Workup

  1. temperaturecooled to room temperature
  2. stirringstirred for 1 hour
  3. filtrationfiltered off
  4. washThe residue was washed with CH2Cl2 (50 mL) and filtrate
  5. extractionwas extracted with CH2Cl2 (3×20 mL)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customto provide crude material, which
  9. customwas purified by flash column chromatography (silica gel; 230-400 mesh; ethyl acetate/hexanes=1:5)

Sources & evidence

ORD record
ord-12c3a54f631f4fd09b39e25be80a64f9
Source dataset
uspto-grants-2015_02
Patent number
US08952021B2

Reaction notes

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