Formaldehyde → 4-(5-{[cis-2,6-Dimethyl-4-morpholinyl]methyl}-1H-tetrazol-1-yl)-2-(trifluoromethyl)benzonitrile

HRID 517766ノート

反応式

HRID 517766 の反応式
[CH2:1]=O.[CH3:3][C@H:4]1[O:9][C@@H:8]([CH3:10])[CH2:7][NH:6][CH2:5]1.C[Si]([N:15]=[N+:16]=[N-:17])(C)C.[N+:18]([C:20]1[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[C:22]([C:28]([F:31])([F:30])[F:29])[CH:21]=1)#[C-:19]>CO>[CH3:10][C@H:8]1[O:9][C@@H:4]([CH3:3])[CH2:5][N:6]([CH2:1][C:19]2[N:18]([C:20]3[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[C:22]([C:28]([F:29])([F:30])[F:31])[CH:21]=3)[N:17]=[N:16][N:15]=2)[CH2:7]1

参加物

6

反応物 4

HCID 712FormaldehydeHCID 78378AzidotrimethylsilaneHCID 6415002,6-Dimethylmorpholine, cis-HCID 251923904-Isocyano-2-(trifluoromethyl)benzonitrile

生成物 1

HCID 566003314-(5-{[cis-2,6-Dimethyl-4-morpholinyl]methyl}-1H-tetrazol-1-yl)-2-(trifluoromethyl)benzonitrile

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

To a solution of formaldehyde (37% in water) (0.114 ml, 1.53 mmol) in methanol (4 ml) was added cis-2,6-dimethylmorpholine (0.188 ml, 1.53 mmol, Alfa Aesar, Ward Hill, USA). The reaction mixture was stirred at room temperature for 2 hours before the addition of trimethylsilylazide (0.203 ml, 1.53 mmol) and 4-isocyano-2-(trifluoromethyl)benzonitrile (300 mg, 1.53 mmol, commercially available from Priaxon, Munich, Germany). The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was partitioned between DCM (50 ml) and water (20 ml). The aqueous layer was extracted with DCM (50 ml). The organic layers were combined, dried over MgSO4, filtered and concentrated. The crude product was purified by flash chromatography (Biotage SP4) using Hexane:EtOAc as an eluant. Relevant fractions were combined and concentrated. This residue was dissolved in MeOH and loaded onto a 5 g SCX cartridge. The cartridge was washed with MeOH and eluted with methanolic ammonia. Relevant fractions were combined and concentrated and the product was left to dry in a vacuum oven overnight. The product was dissolved in 3 ml of DCM and 0.819 ml of 1M HCl in ether was added. The solvent was removed to afford the title compound as a pale yellow solid (340 mg).

後処理

  1. customThe reaction mixture was partitioned between DCM (50 ml) and water (20 ml)
  2. extractionThe aqueous layer was extracted with DCM (50 ml)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by flash chromatography (Biotage SP4)
  7. concentrationconcentrated
  8. dissolutionThis residue was dissolved in MeOH
  9. washThe cartridge was washed with MeOH
  10. washeluted with methanolic ammonia
  11. concentrationconcentrated
  12. waitthe product was left
  13. customto dry in a vacuum oven overnight
  14. dissolutionThe product was dissolved in 3 ml of DCM
  15. addition0.819 ml of 1M HCl in ether was added
  16. customThe solvent was removed

出典と根拠

ORDレコード
ord-8469761d27464bf798a3bee899cbcf74
出典データセット
uspto-grants-2015_08
特許番号
US09115132B2

反応ノート

読み込み中…