Triethylamine → N-[2-bromo-6-chloro-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethylpropyl)phenyl]-4-cyano-3-nitrobenzamide

HRID 1970838Notes

Reaction equation

HRID 1970838 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[NH2:22].C(N(CC)CC)C.[C:30]([C:32]1[CH:40]=[CH:39][C:35]([C:36](O)=[O:37])=[CH:34][C:33]=1[N+:41]([O-:43])=[O:42])#[N:31].O=C1N([ClH]P([ClH]N2CCOC2=O)=O)CCO1>ClCCCl>[Br:1][C:2]1[CH:7]=[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:13])[F:12])[CH:5]=[C:4]([Cl:21])[C:3]=1[NH:22][C:36](=[O:37])[C:35]1[CH:39]=[CH:40][C:32]([C:30]#[N:31])=[C:33]([N+:41]([O-:43])=[O:42])[CH:34]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 221685834-Cyano-3-nitrobenzoic acidHCID 866652762-Bromo-6-chloro-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethyl-propyl)phenylamine

Product 1

HCID 86665275N-[2-bromo-6-chloro-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethylpropyl)phenyl]-4-cyano-3-nitrobenzamideYield 90.1%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a suspension of 2-bromo-6-chloro-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethyl-propyl)phenylamine (Example 3.3) (70 g, 165 mmol) in 1,2-dichloroethane (660 ml) was added triethylamine (50.09 g, 495 mmol), followed by 4-cyano-3-nitrobenzoic acid (made as in WO 2008/074427) (63.4 g, 330 mmol) and bis(2-oxo-3-oxazolidinyl)phosphonic chloride (“BOP-Cl”) (84 g, 330 mmol). The reaction mixture was stirred at 90° C. for 6 hours. The reaction was quenched by addition of aqueous hydrochloric acid (1M) (500 ml) and the phases were separated. The organic phase was washed with saturated aqueous sodium hydrogen carbonate and brine. The aqueous phase was extracted twice with 1,2-dichloroethane. The combined organic extracts were dried over sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 7:3) to give N-[2-bromo-6-chloro-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethylpropyl)phenyl]-4-cyano-3-nitrobenzamide (89 g, 90% yield). 1H NMR (400 MHz, CDCl3): 8.89 (s, 1H), 8.40 (d, 1H), 8.12 (d, 1H), 7.88 (m, 2H), 7.72 (s, 1H).

Workup

  1. customThe reaction was quenched by addition of aqueous hydrochloric acid (1M) (500 ml)
  2. customthe phases were separated
  3. washThe organic phase was washed with saturated aqueous sodium hydrogen carbonate and brine
  4. extractionThe aqueous phase was extracted twice with 1,2-dichloroethane
  5. dry with materialThe combined organic extracts were dried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 7:3)

Sources & evidence

ORD record
ord-84550790dbae4db984330ee02c76310e
Source dataset
uspto-grants-2013_04
Patent number
US08431514B2

Reaction notes

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