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p-Toluenesulfonic acid → (S)-N-((3-Fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)-5-hydroxy-6-nitropicolinamide

HRID 2370832
ノート
印刷プレビュー

反応式

HRID 2370832 の反応式
[F:1][C:2]1[CH:3]=[C:4]([C@@H:13]([C:28]2[C:33]([F:34])=[CH:32][CH:31]=[CH:30][N:29]=2)[NH:14][C:15](=[O:27])[C:16]2[CH:21]=[CH:20][C:19]([O:22]C)=[C:18]([N+:24]([O-:26])=[O:25])[N:17]=2)[CH:5]=[CH:6][C:7]=1[O:8][C:9]([F:12])([F:11])[F:10].[Li+].[Cl-].CC1C=CC(S(O)(=O)=O)=CC=1.CCOC(C)=O>CN1C(=O)CCC1.O>[F:1][C:2]1[CH:3]=[C:4]([C@@H:13]([C:28]2[C:33]([F:34])=[CH:32][CH:31]=[CH:30][N:29]=2)[NH:14][C:15](=[O:27])[C:16]2[CH:21]=[CH:20][C:19]([OH:22])=[C:18]([N+:24]([O-:26])=[O:25])[N:17]=2)[CH:5]=[CH:6][C:7]=1[O:8][C:9]([F:12])([F:10])[F:11]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 6101p-Toluenesulfonic acidHCID 8857Ethyl AcetateHCID 433294Lithium ChlorideHCID 71144173(S)-N-((3-Fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)-5-methoxy-6-nitropicolinamide

生成物 1

HCID 71144193(S)-N-((3-Fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)-5-hydroxy-6-nitropicolinamide

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
180 °C

実験手順

To a stirred solution of (S)—N-((3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)-5-methoxy-6-nitropicolinamide (700 mg, 0.0011 mol) in NMP (7.0 mL) was added LiCl (183.79 mg, 0.0043 mol, Sigma Aldrich, India) followed by pTSA (746.63 mg, 0.0043 mol, Sigma Aldrich, India) at room temperature. The reaction mixture was stirred at 180° C. for 2 h. After completion of the reaction (monitored by TLC, 100% EtOAc), the reaction mixture was cooled to room temperature and water (50 mL) was added and the aqueous solution was extracted with EtOAc (25 mL×2). The organic extracts were washed with water (25 mL×2) and brine (25 mL) and dried over anhydrous sodium sulfate and concentrated. The resulting material was purified by silica gel (60-120 mesh) column chromatography eluting with 60-70% EtOAc in petroleum ether to give the title compound as an off-white solid. 1H-NMR (400 MHz, DMSO-d6): δ 12.77 (br. s., 1H), 9.43 (d, J=7.2 Hz, 1H), 8.57 (d, J=4.4 Hz, 1H), 8.24 (d, J=8.4 Hz, 1H), 7.86-7.79 (m, 2H), 7.59-7.54 (m, 3H), 7.37 (d, J=8.4 Hz, 1H), 6.57 (d, J=7.2 Hz, 1H). MS (ESI, positive ion) m/z: 471 (M+H).

後処理

  1. temperaturethe reaction mixture was cooled to room temperature
  2. extractionthe aqueous solution was extracted with EtOAc (25 mL×2)
  3. washThe organic extracts were washed with water (25 mL×2) and brine (25 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customThe resulting material was purified by silica gel (60-120 mesh) column chromatography
  7. washeluting with 60-70% EtOAc in petroleum ether

出典と根拠

ORDレコード
ord-f7c75e962c8041f5acfb42c3469ce2ca
出典データセット
uspto-grants-2014_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08710043B2

反応ノート

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