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

HRID 409036노트

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HRID 409036 반응식
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]

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-b92249f02b9849549ab3da85990781ce
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759372B2

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