Acetonitrile → (Z)-(S)-4-[(S)-1-(2,6-difluoropyridin-3-yl)ethyl]-2-[1-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]methylidene]-6-methylmorpholin-3-one

HRID 16342

反応式

HRID 16342 の反応式
[Br-].C1([PH+](C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(#N)C.[F:24][C:25]1[C:30]([C@@H:31]([N:33]2[CH2:38][CH:37]([CH3:39])[O:36][C@H:35](O)[C:34]2=[O:41])[CH3:32])=[CH:29][CH:28]=[C:27]([F:42])[N:26]=1.[CH3:43][O:44][C:45]1[CH:46]=[C:47]([CH:50]=[CH:51][C:52]=1[N:53]1[CH:57]=[C:56]([CH3:58])[N:55]=[CH:54]1)[CH:48]=O>C(N(CC)CC)C>[F:24][C:25]1[C:30]([C@@H:31]([N:33]2[CH2:38][C@H:37]([CH3:39])[O:36]/[C:35](=[CH:48]\[C:47]3[CH:50]=[CH:51][C:52]([N:53]4[CH:57]=[C:56]([CH3:58])[N:55]=[CH:54]4)=[C:45]([O:44][CH3:43])[CH:46]=3)/[C:34]2=[O:41])[CH3:32])=[CH:29][CH:28]=[C:27]([F:42])[N:26]=1

参加物

6

反応物 4

HCID 6342AcetonitrileHCID 517696Phosphine, triphenyl-, hydrobromideHCID 272824453-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzaldehydeHCID 68717852(S)-4-[(S)-1-(2,6-difluoropyridin-3-yl)ethyl]-2-hydroxy-6-methylmorpholin-3-one

生成物 1

HCID 16738921(Z)-(S)-4-[(S)-1-(2,6-difluoropyridin-3-yl)ethyl]-2-[1-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]methylidene]-6-methylmorpholin-3-one収率 56.6%

試薬・触媒・溶媒 1

HCID 8471Triethylamine溶媒

実験手順

Triphenylphosphonium bromide (6.52 g) was added to an acetonitrile solution of (S)-4-[(S)-1-(2,6-difluoropyridin-3-yl)ethyl]-2-hydroxy-6-methylmorpholin-3-one (4.3 g). The resulting reaction solution was heated under reflux for 1 hr, and triethylamine (5.28 mL) and 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzaldehyde (3.42 g) were added thereto. The resulting reaction solution was heated under reflux for 1.5 hr and concentrated under reduced pressure. The residue was diluted with a 2 N hydrochloric acid aqueous solution and ethyl acetate. The water layer was separated, and the organic layer was washed with a 2 N hydrochloric acid aqueous solution. All the water layers were combined and alkalinized with a concentrated sodium hydroxide aqueous solution. The alkaline aqueous solution was extracted with ethyl acetate. The organic layer was separated, washed with saturated sodium hydrogencarbonate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (carrier: Chromatorex NH, eluting solvent; heptane:ethyl acetate=1:1 to 0:1) to give 4.06 g of the title compound. The physical property values of this compound were as follows:

後処理

  1. customThe resulting reaction solution
  2. temperaturewas heated
  3. temperatureunder reflux for 1 hr
  4. customThe resulting reaction solution
  5. temperaturewas heated
  6. temperatureunder reflux for 1.5 hr
  7. concentrationconcentrated under reduced pressure
  8. additionThe residue was diluted with a 2 N hydrochloric acid aqueous solution and ethyl acetate
  9. customThe water layer was separated
  10. washthe organic layer was washed with a 2 N hydrochloric acid aqueous solution
  11. extractionThe alkaline aqueous solution was extracted with ethyl acetate
  12. customThe organic layer was separated
  13. washwashed with saturated sodium hydrogencarbonate
  14. dry with materialdried over anhydrous magnesium sulfate
  15. concentrationconcentrated under reduced pressure
  16. customThe residue was purified by silica gel column chromatography (carrier: Chromatorex NH, eluting solvent; heptane:ethyl acetate=1:1 to 0:1)

出典と根拠

ORDレコード
ord-988d3b53c8d44d60b87cd065433bd4e4
出典データセット
uspto-grants-2010_06
特許番号
US07737141B2

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