Pyridine → 3-cyano-N-[2,6-dimethyl-4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-phenyl]-5-nitro-benzamide

HRID 888459

Reaction equation

HRID 888459 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([N+:12]([O-:14])=[O:13])[CH:11]=1)[C:6]([OH:8])=O)#[N:2].C(Cl)(=O)C(Cl)=O.[CH3:21][C:22]1[CH:28]=[C:27]([C:29]([F:38])([C:34]([F:37])([F:36])[F:35])[C:30]([F:33])([F:32])[F:31])[CH:26]=[C:25]([CH3:39])[C:23]=1[NH2:24].N1C=CC=CC=1.FC1C=CC([N+]([O-])=O)=CC=1C(Cl)=O.C(=O)([O-])O.[Na+]>ClCCl.O1CCCC1.CN(C)C=O>[C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([N+:12]([O-:14])=[O:13])[CH:11]=1)[C:6]([NH:24][C:23]1[C:25]([CH3:39])=[CH:26][C:27]([C:29]([F:38])([C:30]([F:31])([F:32])[F:33])[C:34]([F:35])([F:36])[F:37])=[CH:28][C:22]=1[CH3:21])=[O:8])#[N:2]

Participants

10

Reactant 6

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 98824254-(1,1,1,2,3,3,3-Heptafluoropropan-2-yl)-2,6-dimethylanilineHCID 109765702-Fluoro-5-nitrobenzoyl chlorideHCID 219425653-Cyano-5-nitrobenzoic acid

Product 1

HCID 592269403-cyano-N-[2,6-dimethyl-4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-phenyl]-5-nitro-benzamideYield 77%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 3-cyano-5-nitro-benzoic acid (Example I4) (7.2 g, 37.5 mmol) in dichloromethane (40 ml) was added oxalyl chloride (3.808 ml, 45 mmol) at ambient temperature, followed by N,N-dimethylformamide (“DMF”) (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 to residue was suspended in tetrahydrofuran (50 ml). 2,6-dimethyl-4-(heptafluoro-prop-2-yl)-aniline (9.761 g, 33.7 mmol) (prepared according to EP 1,006,102) was dissolved in tetrahydrofuran (50 ml) and pyridine (6.035 ml, 75 mmol) was added. The mixture was cooled to 0° C. and the solution of 2-fluoro-5-nitro-benzoyl chloride was added. The reaction mixture was stirred at ambient temperature for 12 hours. Then aqueous sodium hydrogen carbonate (saturated) (100 ml) was added and the organic phase 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 6:1) to give 3-cyano-N-[2,6-dimethyl-4-(1,2,2,2-tetrafluoro-1-trifluoromethyl-ethyl)-phenyl]-5-nitro-benzamide (12 g, 77% yield). 1H-NMR (400 MHz, CDCl3): 8.99 (m, 1H), 8.72 (m, 1H), 8.6 (m, 1H), 7.80 (s, 1H), 7.4 (s, 2H), 2.33 (s, 6H) ppm.

Workup

  1. temperatureheated
  2. temperatureto reflux for 3 hours
  3. temperatureto cool to ambient temperature
  4. concentrationconcentrated
  5. temperatureThe mixture was cooled to 0° C.
  6. stirringThe reaction mixture was stirred at ambient temperature for 12 hours
  7. extractionthe organic phase extracted twice with ethyl acetate (2×200 ml)
  8. dry with materialThe combined organic extracts were dried over sodium sulfate
  9. concentrationconcentrated
  10. customThe residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 6:1)

Sources & evidence

ORD record
ord-f8dc4f2d815b4f7489ab5cc90dde99de
Source dataset
uspto-grants-2012_08
Patent number
US08247594B2

Linked notes

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