Water → HCID 178456684、化合物

HRID 1498553ノート

反応式

HRID 1498553 の反応式
Cl.[CH2:2]([O:9][C:10]1[CH:18]=[CH:17][C:13]([C:14]([NH2:16])=[NH:15])=[C:12]([F:19])[CH:11]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(=O)([O-])O.[K+].O.Cl[CH2:27][C:28]([C:30]1[N:31]([CH:35]([CH3:37])[CH3:36])[N:32]=[CH:33][N:34]=1)=O>C1COCC1.[Na+].[Cl-]>[CH2:2]([O:9][C:10]1[CH:18]=[CH:17][C:13]([C:14]2[NH:16][CH:27]=[C:28]([C:30]3[N:31]([CH:35]([CH3:37])[CH3:36])[N:32]=[CH:33][N:34]=3)[N:15]=2)=[C:12]([F:19])[CH:11]=1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

参加物

7

反応物 4

HCID 962WaterHCID 516893Potassium BicarbonateHCID 197001614-Benzyloxy-2-fluoro-benzamidine hydrochlorideHCID 712991852-chloro-1-(1-isopropyl-1H-1,2,4-triazol-5-yl)ethanone

生成物 1

HCID 178456684HCID 178456684、化合物収率 84%

試薬・触媒・溶媒 2

HCID 5234Sodium Chloride溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

A solution of 4-benzyloxy-2-fluoro-benzamidine hydrochloride (74.5 g, 0.265 mol) in THF (705 mL) was treated with potassium hydrogen carbonate (106 g, 1.06 mol) and H2O (150 mL). The resultant mixture was heated to reflux to give a white suspension. Whilst maintaining gentle reflux and mechanical stirring (500 rpm) a solution of 2-chloro-1-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-ethanone (50 g, 0.265 mol) was added dropwise over 40 min. The resultant suspension gradually dissolved giving a dark red mixture that was refluxed for 18 h. The mixture was cooled to RT, diluted with saturated aqueous NaCl solution (500 mL) and extracted with EtOAc (500 mL). The organic extract was washed with saturated aqueous NaCl solution, dried over Na2SO4, filtered and concentrated in vacuo to give a pink solid The solid was triturated in a mixture of MTBE/pentane (1:1 by volume, 300 mL), collected by filtration, washed with a MTBE/pentane mixture and dried in vacuo to give 5-[2-(4-Benzyloxy-2-fluoro-phenyl)-1H-imidazol-4-yl]-1-isopropyl-1H-[1,2,4]triazole as a pale pink solid (84 g, 84%). 1H NMR (400 MHz, d6-DMSO): 7.95-7.93 (2 H, m), 7.76 (1 H, s), 7.44-7.42 (5 H, m), 7.12 (1 H, dd, J=13.10, 2.52 Hz), 7.03 (1 H, dd, J=8.74, 2.47 Hz), 5.90 (1 H, m), 5.21 (2 H, s), 1.46 (6 H, d, J=6.60 Hz).

後処理

  1. temperatureto reflux
  2. customto give a white suspension
  3. temperatureWhilst maintaining gentle
  4. temperaturereflux
  5. additionwas added dropwise over 40 min
  6. customgiving a dark red mixture that
  7. temperaturewas refluxed for 18 h
  8. extractionextracted with EtOAc (500 mL)
  9. extractionThe organic extract
  10. washwas washed with saturated aqueous NaCl solution
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customto give a pink solid The solid
  15. customwas triturated in a mixture of MTBE/pentane (1:1 by volume, 300 mL)
  16. filtrationcollected by filtration
  17. washwashed with a MTBE/pentane mixture
  18. customdried in vacuo

出典と根拠

ORDレコード
ord-430e27520dde443fb8c9462505f28745
出典データセット
uspto-grants-2015_12
特許番号
US09198918B2

反応ノート

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