HCID 86711207、化合物 → HCID 86711208、化合物

HRID 1850790ノート

反応式

HRID 1850790 の反応式
[F:1][C:2]1[CH:21]=[C:20]([S:22]([CH3:25])(=[O:24])=[O:23])[CH:19]=[CH:18][C:3]=1[O:4][CH2:5][CH2:6][C@@H:7]1[CH2:9][C@@H:8]1[CH:10]1[CH2:15][CH2:14][N:13]([C:16]#[N:17])[CH2:12][CH2:11]1.[OH:26][NH:27][C:28](=N)[CH2:29][O:30][CH3:31]>O1CCCC1.[Cl-].[Zn+2].[Cl-]>[F:1][C:2]1[CH:21]=[C:20]([S:22]([CH3:25])(=[O:23])=[O:24])[CH:19]=[CH:18][C:3]=1[O:4][CH2:5][CH2:6][C@H:7]1[CH2:9][C@H:8]1[CH:10]1[CH2:11][CH2:12][N:13]([C:16]2[O:26][N:27]=[C:28]([CH2:29][O:30][CH3:31])[N:17]=2)[CH2:14][CH2:15]1

参加物

5

反応物 2

HCID 86711207HCID 86711207、化合物HCID 178496050HCID 178496050、化合物

生成物 1

HCID 86711208HCID 86711208、化合物

試薬・触媒・溶媒 2

HCID 3007855Zincchloride触媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 4-((1R,2S)-2-{2-{2-fluoro-4-(methylsulfonyl)phenoxy]ethyl}cyclopropyl)piperidine-1-carbonitrile (Step D, Example 111; 100 mg, 0.27 mmol) and N-hydroxy-2-methoxyacetimidamide (38 mg, 0.37 mmol) in tetrahydrofuran (5 mL) was added zinc chloride (0.8 mL, 0.5 M in tetrahydrofuran, 0.4 mmol). The mixture was refluxed for 2 h, cooled to RT, and concentrated to dryness under reduced pressure. The residue was dissolved in 2 mL of 4N HCl ethanol and water (1:1). The solution was refluxed for 30 min, cooled to RT, and concentrated to dryness under reduced pressure. The residue was dissolved in methanol (5 mL), neutralized by the addition of excess potassium carbonate, mixed silica gel (2 g), and concentrated to dryness under reduced pressure. The residue was loaded on a silica gel column (10 g of silica gel) and eluted with a gradient of dichloromethane/CMA, 19:1, 500 mL; 4:1, 500 mL to provide the title compound. MS (ESI) m/z 454 [M+H]+.

後処理

  1. temperatureThe mixture was refluxed for 2 h
  2. concentrationconcentrated to dryness under reduced pressure
  3. dissolutionThe residue was dissolved in 2 mL of 4N HCl ethanol
  4. temperatureThe solution was refluxed for 30 min
  5. temperaturecooled to RT
  6. concentrationconcentrated to dryness under reduced pressure
  7. dissolutionThe residue was dissolved in methanol (5 mL)
  8. additionneutralized by the addition of excess potassium carbonate
  9. additionmixed silica gel (2 g)
  10. concentrationconcentrated to dryness under reduced pressure
  11. washeluted with a gradient of dichloromethane/CMA, 19:1, 500 mL

出典と根拠

ORDレコード
ord-4ca24d07ce524cad8ca603b7e6b8a939
出典データセット
uspto-grants-2015_02
特許番号
US08957062B2

反応ノート

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