Pyridine → 4-cyano-N-[2-ethyl-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethyl-propyl)-6-methyl-phenyl]-3-methyl-benzamide

HRID 245129ノート

反応式

HRID 245129 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[CH3:12])#[N:2].C(Cl)(=O)C(Cl)=O.[CH3:19][C:20]1[CH:26]=[C:25]([C:27]([F:36])([C:32]([F:35])([F:34])[F:33])[C:28](F)([F:30])[F:29])[CH:24]=[C:23]([CH2:37][CH3:38])[C:21]=1[NH2:22].N1C=CC=CC=1.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:22][C:21]2[C:20]([CH3:19])=[CH:26][C:25]([C:27]([F:36])([C:32]([F:33])([F:34])[F:35])[C:28]([F:30])([F:29])[C:32]([F:35])([F:34])[F:33])=[CH:24][C:23]=2[CH2:37][CH3:38])=[O:9])=[CH:5][C:4]=1[CH3:12])#[N:2]

参加物

9

反応物 5

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 102410994-Cyano-3-methylbenzoic acidHCID 227346102-Methyl-6-ethyl-4-(heptafluoro-prop-2-yl)-aniline

生成物 1

HCID 866535934-cyano-N-[2-ethyl-4-(1,2,2,3,3,3-hexafluoro-1-trifluoromethyl-propyl)-6-methyl-phenyl]-3-methyl-benzamide収率 200%

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 solution of 4-cyano-3-methyl-benzoic acid (6.64 g, 41.20 mmol) (prepared according to Bioorganic & Medicinal Chemistry Letters 2004, 14(17), 4585-4589 or EP 1,512,687) and N,N-dimethylformamide (“DMF”) (few drops) in dichloromethane (200 ml) under an atmosphere of nitrogen was added oxalyl chloride (4.18 ml, 49.44 mmol). The reaction mixture was stirred for one hour at ambient temperature and then for 1.5 hours at 60° C. The reaction mixture was concentrated and the residue dissolved in tetrahydrofuran (200 ml). The solution was added drop-wise to a solution of 2-methyl-6-ethyl-4-(heptafluoro-prop-2-yl)-aniline (prepared according to EP 1,006,102) (10.910 g, 30.90 mmol) and pyridine (3.31 ml, 41.20 mmol) in tetrahydrofuran (200 ml). The reaction mixture was stirred for 16 hours at 90° C. Then the reaction mixture was poured into aqueous sodium hydrogen carbonate (1M) and the mixture extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated. The residue was purified by column chromatography (eluent: ethyl acetate/cyclohexane 1:3) to give the desired compound (15.34 g, 94% yield). 1H-NMR (400 MHz, CDCl3): 7.90 (1H, s), 7.78 (2H, m), 7.53 (1H, s), 7.39 (2H, s), 2.67 (5H, s), 2.35 (3H, s), 1.16 (3H, t) ppm.

後処理

  1. waitfor 1.5 hours at 60° C
  2. concentrationThe reaction mixture was concentrated
  3. dissolutionthe residue dissolved in tetrahydrofuran (200 ml)
  4. stirringThe reaction mixture was stirred for 16 hours at 90° C
  5. extractionthe mixture extracted three times with ethyl acetate
  6. dry with materialThe combined organic phases were dried over sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography (eluent: ethyl acetate/cyclohexane 1:3)

出典と根拠

ORDレコード
ord-a3d7edd9df2c4f25a628159f7d62059e
出典データセット
uspto-grants-2014_02
特許番号
US08658698B2

反応ノート

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