Pyridine → 4-cyano-N-[2,6-dibromo-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethylpropyl)phenyl]-3-nitrobenzamide

HRID 1970840ノート

反応式

HRID 1970840 の反応式
[C:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[CH:5][C:4]=1[N+:12]([O-:14])=[O:13])#[N:2].C(Cl)(=O)C(Cl)=O.[Br:21][C:22]1[CH:27]=[C:26]([C:28]([F:40])([C:36]([F:39])([F:38])[F:37])[C:29]([F:35])([F:34])[C:30]([F:33])([F:32])[F:31])[CH:25]=[C:24]([Br:41])[C:23]=1[NH2:42].N1C=CC=CC=1.C(C1C=CC(C(Cl)=O)=CC=1[N+]([O-])=O)#N.C(=O)([O-])O.[Na+]>ClCCl.O1CCCC1.CN(C)C=O>[C:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]([NH:42][C:23]2[C:24]([Br:41])=[CH:25][C:26]([C:28]([F:40])([C:36]([F:37])([F:38])[F:39])[C:29]([F:34])([F:35])[C:30]([F:31])([F:32])[F:33])=[CH:27][C:22]=2[Br:21])=[O:9])=[CH:5][C:4]=1[N+:12]([O-:14])=[O:13])#[N:2]

参加物

10

反応物 6

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 214065294-Cyano-3-nitrobenzoyl chlorideHCID 221685834-Cyano-3-nitrobenzoic acidHCID 582974122,6-Dibromo-4-(perfluorobutan-2-yl)aniline

生成物 1

HCID 867618164-cyano-N-[2,6-dibromo-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethylpropyl)phenyl]-3-nitrobenzamide収率 37.1%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a suspension of 4-cyano-3-nitrobenzoic acid (prepared as described in WO 2008/074427) (30 g, 156 mmol) in dichloromethane (150 ml) was added oxalyl chloride (15.88 ml, 187 mmol) at ambient temperature, followed by N,N-dimethylformamide (“DMF”) (0.2 ml). The reaction mixture was stirred for 30 minutes at ambient temperature and then heated to reflux for 30 minutes. The reaction mixture was allowed to cool to ambient temperature, concentrated and the residue was suspended in tetrahydrofuran (150 ml). A solution of 2,6-dibromo-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethylpropyl)-phenylamine (Example 3.2) (55 g, 117.3 mmol) in a mixture of tetrahydrofuran (150 ml) and pyridine (12.57 ml, 156.4 mmol) was cooled to 0° C. and the solution of 4-cyano-3-nitrobenzoyl chloride was added. The reaction mixture was stirred at ambient temperature for 12 hours. Satruated aqueous sodium hydrogen carbonate (300 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 4:1) to give 4-cyano-N-[2,6-dibromo-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethylpropyl)phenyl]-3-nitrobenzamide (28 g, 37% yield). LC-MS (Method 2): RT=2.24, [M−H]−=642.

後処理

  1. temperatureheated
  2. temperatureto reflux for 30 minutes
  3. temperatureto cool to ambient temperature
  4. concentrationconcentrated
  5. temperaturewas 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 4:1)

出典と根拠

ORDレコード
ord-3aef3c93e4ac4e10a2f84ab0afa073c5
出典データセット
uspto-grants-2013_04
特許番号
US08431514B2

反応ノート

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