Pyridine → 4-cyano-N-[2,6-dichloro-3-fluoro-4-(1,2,2,2-tetrafluoro-1-trifluoromethylethyl)phenyl]-3-nitrobenzamide

HRID 1970839Notes

Reaction equation

HRID 1970839 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[C:6]([C:9]([F:18])([C:14]([F:17])([F:16])[F:15])[C:10]([F:13])([F:12])[F:11])[CH:5]=[C:4]([Cl:19])[C:3]=1[NH2:20].[C:21]([C:23]1[CH:31]=[CH:30][C:26]([C:27](O)=[O:28])=[CH:25][C:24]=1[N+:32]([O-:34])=[O:33])#[N:22].N1C=CC=CC=1.O=C1N([ClH]P([ClH]N2CCOC2=O)=O)CCO1>ClCCl>[C:21]([C:23]1[CH:31]=[CH:30][C:26]([C:27]([NH:20][C:3]2[C:4]([Cl:19])=[CH:5][C:6]([C:9]([F:18])([C:10]([F:12])([F:13])[F:11])[C:14]([F:15])([F:16])[F:17])=[C:7]([F:8])[C:2]=2[Cl:1])=[O:28])=[CH:25][C:24]=1[N+:32]([O-:34])=[O:33])#[N:22]

Participants

5

Reactant 3

HCID 1049PyridineHCID 221685834-Cyano-3-nitrobenzoic acidHCID 866652782,6-Dichloro-3-fluoro-4-(1,2,2,2-tetrafluoro-1-trifluoromethylethyl)-phenylamine

Product 1

HCID 866652774-cyano-N-[2,6-dichloro-3-fluoro-4-(1,2,2,2-tetrafluoro-1-trifluoromethylethyl)phenyl]-3-nitrobenzamideYield 91.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2,6-dichloro-3-fluoro-4-(1,2,2,2-tetrafluoro-1-trifluoromethylethyl)-phenylamine (Example 3.2) (3.48 g, 10 mmol) and 4-cyano-3-nitrobenzoic acid (made as in WO 2008/074427) (3.84 g, 20 mmol) in dichloromethane (40 ml) was added pyridine (4.17 ml, 30 mmol) and bis(2-oxo-3-oxazolidinyl)phosphonic chloride (“BOP-Cl”) (5.09 g, 20 mmol). The reaction mixture was heated to reflux for 6 hours. The reaction mixture was cooled to ambient temperature and quenched by addition of aqueous hydrochloric acid (1N) (50 ml). The mixture was then extracted three times with dichloromethane. The combined organic extracts were washed with saturated aqueous sodium hydrogen carbonate, dried over sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent:cyclohexane/ethyl acetate 7:3) to give 4-cyano-N-[2,6-dichloro-3-fluoro-4-(1,2,2,2-tetrafluoro-1-trifluoromethylethyl)phenyl]-3-nitrobenzamide (4.76 g, 91% yield). LC-MS (Method 2): RT=2.08, [M−H]−=520.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 6 hours
  3. customquenched by addition of aqueous hydrochloric acid (1N) (50 ml)
  4. extractionThe mixture was then extracted three times with dichloromethane
  5. washThe combined organic extracts were washed with saturated aqueous sodium hydrogen carbonate
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography on silica gel (eluent:cyclohexane/ethyl acetate 7:3)

Sources & evidence

ORD record
ord-6dd833e5368c48348db6785cd072e554
Source dataset
uspto-grants-2013_04
Patent number
US08431514B2

Reaction notes

Loading…