Sodium Hydroxide → 3-amino-N-[2-bromo-6-chloro-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethylpropyl)phenyl]-4-cyanobenzamide

HRID 1970841Notes

Reaction equation

HRID 1970841 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([C:8]([F:20])([C:16]([F:19])([F:18])[F:17])[C:9]([F:15])([F:14])[C:10]([F:13])([F:12])[F:11])[CH:5]=[C:4]([Cl:21])[C:3]=1[NH:22][C:23](=[O:35])[C:24]1[CH:29]=[CH:28][C:27]([C:30]#[N:31])=[C:26]([N+:32]([O-])=O)[CH:25]=1.[OH-].[Na+].S(S([O-])=O)([O-])=O.[Na+].[Na+]>O1CCCC1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[NH2:32][C:26]1[CH:25]=[C:24]([CH:29]=[CH:28][C:27]=1[C:30]#[N:31])[C:23]([NH:22][C:3]1[C:4]([Cl:21])=[CH:5][C:6]([C:8]([F:20])([C:16]([F:17])([F:18])[F:19])[C:9]([F:14])([F:15])[C:10]([F:11])([F:12])[F:13])=[CH:7][C:2]=1[Br:1])=[O:35]

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 24489Sodium DithioniteHCID 86665275N-[2-bromo-6-chloro-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethylpropyl)phenyl]-4-cyano-3-nitrobenzamide

Product 1

HCID 866652793-amino-N-[2-bromo-6-chloro-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethylpropyl)phenyl]-4-cyanobenzamideYield 78.4%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of N-[2-bromo-6-chloro-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethyl-propyl)phenyl]-4-cyano-3-nitrobenzamide (Example 1.1) (92.7 g, 154.8 mmol) in tetrahydrofuran (800 ml) was added aqueous sodium hydroxide (0.1 M) (270 ml), sodium hydrosulfite (80.9 g, 464.4 mmol) and tetrabutylammonium bromide (“TBAB”) (4.99 g, 15.5 mmol). The reaction mixture was stirred at ambient temperature for 90 minutes. The phases were separated. The aqueous phase was extracted twice with ethyl acetate. The combined organic extracts were washed with water, aqueous sodium hydrogen carbonate (10% w/v) (400 ml) and brine, dried over sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent:cyclohexane/ethyl acetate 5:1) to give 3-amino-N-[2-bromo-6-chloro-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethylpropyl)phenyl]-4-cyanobenzamide (69 g, 78.4% yield). 1H NMR (400 MHz, CDCl3): 7.82 (s, 1H), 7.75 (s, 1H), 7.71 (s, 1H), 7.51 (m, 1H), 7.35 (s, 1H), 7.21 (m, 1H), 4.7 (s, 2H).

Workup

  1. customThe phases were separated
  2. extractionThe aqueous phase was extracted twice with ethyl acetate
  3. washThe combined organic extracts were washed with water, aqueous sodium hydrogen carbonate (10% w/v) (400 ml) and brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography on silica gel (eluent:cyclohexane/ethyl acetate 5:1)

Sources & evidence

ORD record
ord-c16818541bc244f5a1cb4fcb41dc4ba4
Source dataset
uspto-grants-2013_04
Patent number
US08431514B2

Reaction notes

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