Sodium Azide → (5S,6S,9R)-5-azido-6-(2,3-difluorophenyl)-9-(triisopropylsilyloxy)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine

HRID 1879367ノート

反応式

HRID 1879367 の反応式
Cl[C@H:2]1[C:12]2[C:7](=[N:8][CH:9]=[CH:10][CH:11]=2)[C@H:6]([O:13][Si:14]([CH:21]([CH3:23])[CH3:22])([CH:18]([CH3:20])[CH3:19])[CH:15]([CH3:17])[CH3:16])[CH2:5][CH2:4][C@H:3]1[C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[C:25]=1[F:31].[N-:32]=[N+:33]=[N-:34].[Na+]>CN(C)C=O.O.C(OCC)(=O)C>[N:32]([C@@H:2]1[C:12]2[C:7](=[N:8][CH:9]=[CH:10][CH:11]=2)[C@H:6]([O:13][Si:14]([CH:21]([CH3:23])[CH3:22])([CH:18]([CH3:20])[CH3:19])[CH:15]([CH3:17])[CH3:16])[CH2:5][CH2:4][C@H:3]1[C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[C:25]=1[F:31])=[N+:33]=[N-:34]

参加物

6

反応物 2

HCID 33557Sodium AzideHCID 67115927(5R,6S,9R)-5-chloro-6-(2,3-difluorophenyl)-9-(triisopropylsilyloxy)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine

生成物 1

HCID 71533837(5S,6S,9R)-5-azido-6-(2,3-difluorophenyl)-9-(triisopropylsilyloxy)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

In a 100 mL round-bottom flask was dissolved (5R,6S,9R)-5-chloro-6-(2,3-difluorophenyl)-9-(triisopropylsilyloxy)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine (566 mg, 1.214 mmol) in dimethylformamide (5 mL) to give a colorless solution. Sodium azide (474 mg, 7.29 mmol) was added, and the mixture was stirred at room temperature under nitrogen for 2.5 h. LCMS indicated only partial reaction. The mixture was heated at 50° C. overnight. After 15 h, LCMS indicated complete conversion with some elimination product. The mixture was diluted with water and ethyl acetate. The layers were separated. The organic layer was washed with brine, dried, and concentrated to give a colorless oil. The crude product was carried onto the next reaction without further purification and characterization. Smaller scale purification afforded an analytical sample: MS(ESI)[M+H+]=473.27; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.52-8.63 (m, 1H) 7.75 (d, J=7.81 Hz, 1H) 7.23-7.36 (m, 1H) 6.95-7.17 (m, 2H) 6.89 (br. s., 1H) 5.28 (d, J=4.03 Hz, 1H) 4.90 (d, J=9.07 Hz, 1H) 3.79 (t, J=9.44 Hz, 1H) 1.86-2.23 (m, 4H) 1.16-1.30 (m, 3H) 0.98-1.15 (m, 18H); 19F NMR (376 MHz, CHLOROFORM-d) δ ppm −137.68-−137.36 (m, 1F) −141.78-−141.54 (m, 1F).

後処理

  1. customto give a colorless solution
  2. customreaction
  3. temperatureThe mixture was heated at 50° C. overnight
  4. waitAfter 15 h
  5. customThe layers were separated
  6. washThe organic layer was washed with brine
  7. customdried
  8. concentrationconcentrated
  9. customto give a colorless oil
  10. customSmaller scale purification
  11. customafforded an analytical sample

出典と根拠

ORDレコード
ord-087f93b15dbe4daa81ef1943f441ea6b
出典データセット
uspto-grants-2012_11
特許番号
US08314117B2

反応ノート

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