Pyridine → N-[2-Ethyl-6-methyl-4-(1,1,1,2,3,3,4,4,4-nonafluorobutan-2-yl)phenyl]-2-fluoro-3-nitrobenzamide

HRID 570755

Reaction equation

HRID 570755 reaction equation
[F:1][C:2]1[C:10]([N+:11]([O-:13])=[O:12])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.C(Cl)(=O)C(Cl)=O.[CH2:20]([C:22]1[CH:28]=[C:27]([C:29]([F:41])([C:37]([F:40])([F:39])[F:38])[C:30]([F:36])([F:35])[C:31]([F:34])([F:33])[F:32])[CH:26]=[C:25]([CH3:42])[C:23]=1[NH2:24])[CH3:21].N1C=CC=CC=1>ClCCl.O1CCCC1.CN(C)C=O>[CH2:20]([C:22]1[CH:28]=[C:27]([C:29]([F:41])([C:37]([F:38])([F:39])[F:40])[C:30]([F:35])([F:36])[C:31]([F:32])([F:33])[F:34])[CH:26]=[C:25]([CH3:42])[C:23]=1[NH:24][C:4](=[O:6])[C:3]1[CH:7]=[CH:8][CH:9]=[C:10]([N+:11]([O-:13])=[O:12])[C:2]=1[F:1])[CH3:21]

Participants

8

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 186729922-Fluoro-3-nitrobenzoic acidHCID 866652892-Ethyl-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethylpropyl)-6-methylaniline

Product 1

HCID 86673887N-[2-Ethyl-6-methyl-4-(1,1,1,2,3,3,4,4,4-nonafluorobutan-2-yl)phenyl]-2-fluoro-3-nitrobenzamideYield 43%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 2-fluoro-3-nitrobenzoic acid (6.3 g, 34 mmol) in dichloromethane (20 ml) was added oxalyl chloride (4.3 ml) at ambient temperature, followed by N,N-dimethylformamide (0.2 ml). The reaction mixture was stirred for 1 hour at ambient temperature and then heated to reflux for 3 hours. The reaction mixture was allowed to cool to ambient temperature and then concentrated. The residue was suspended in tetrahydrofuran (50 ml). 2-Ethyl-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethylpropyl)-6-methylaniline (preparation as described in WO 08/074427) (10 g, 28.3 mmol) was dissolved in tetrahydrofuran (50 ml) and pyridine (6.8 ml, 84.9 mmol) was added. The reaction mixture was stirred at ambient temperature for 3 hours, then at reflux for 3 hours. The reaction was quenched by addition of saturated aqueous sodium hydrogen carbonate (100 ml) and the mixture extracted twice with ethyl acetate (2×200 ml). 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 4:1 to 0:1) to give N-[2-ethyl-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethylpropyl)-6-methylphenyl]-2-fluoro-3-nitrobenzamide (6.32 g, 43% yield).

Workup

  1. temperatureheated
  2. temperatureto reflux for 3 hours
  3. temperatureto cool to ambient temperature
  4. concentrationconcentrated
  5. stirringThe reaction mixture was stirred at ambient temperature for 3 hours
  6. temperatureat reflux for 3 hours
  7. customThe reaction was quenched by addition of saturated aqueous sodium hydrogen carbonate (100 ml)
  8. extractionthe mixture extracted twice with ethyl acetate (2×200 ml)
  9. dry with materialThe combined organic extracts were dried over sodium sulfate
  10. concentrationconcentrated
  11. customThe residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 4:1 to 0:1)

Sources & evidence

ORD record
ord-adcd363535784219a3538c2830e1d944
Source dataset
uspto-grants-2015_05
Patent number
US09023873B2

Linked notes

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