N'-Hydroxy-4-methylbenzenecarboximidamide → 5-(3-Tert-butyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-7-yl)-3-(p-tolyl)-1,2,4-oxadiazole

HRID 2047646ノート

反応式

HRID 2047646 の反応式
[CH3:1][C:2]1[CH:11]=[CH:10][C:5]([C:6](=[N:8][OH:9])[NH2:7])=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].[C:18]([C:22]1[N:26]2[CH2:27][CH2:28][CH:29]([C:31](OCC)=O)[CH2:30][C:25]2=[N:24][N:23]=1)([CH3:21])([CH3:20])[CH3:19].C(=O)(O)[O-].[Na+]>O1CCCC1.C(OCC)(=O)C>[C:18]([C:22]1[N:26]2[CH2:27][CH2:28][CH:29]([C:31]3[O:9][N:8]=[C:6]([C:5]4[CH:4]=[CH:3][C:2]([CH3:1])=[CH:11][CH:10]=4)[N:7]=3)[CH2:30][C:25]2=[N:24][N:23]=1)([CH3:21])([CH3:19])[CH3:20]

参加物

7

反応物 4

HCID 209113N'-Hydroxy-4-methylbenzenecarboximidamideHCID 516892Sodium BicarbonateHCID 23665647Potassium tert-butoxideHCID 67300535Ethyl 3-t-butyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-7-carboxylate

生成物 1

HCID 673002765-(3-Tert-butyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-7-yl)-3-(p-tolyl)-1,2,4-oxadiazole収率 49%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

Add 4-methylbenzamidoxime (1.44 g, 9.3 mmol) to a 1M solution of potassium tert-butoxide (8.6 mL, 8.6 mmol) diluted with tetrahydrofuran (120 mL). Add ethyl 3-t-butyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-7-carboxylate (2.0 g, 7.2 mmol) and stir overnight at room temperature. Dissolve the reaction in a 1:1 mixture of half saturated aqueous sodium bicarbonate and ethyl acetate. Separate the phases and extract the aqueous phase with ethyl acetate. Wash the combined organic layers with aqueous saturated sodium chloride, dry over anhydrous sodium sulfate, filter, and concentrate under reduced pressure. Purify the resulting residue by silica gel flash chromatography eluting with 25-100% ethyl acetate:hexane followed by 5% methanol:ethyl acetate. Recrystallize from dichloromethane and hexane to afford the title compound as a white solid (1.19 g). 1H NMR (CDCl3) δ 1.46 (s, 9H), 2.4 (s, 4H), 2.59 (m, 1H), 3.4 (m, 1H), 3.54-3.69 (m, 2H), 4.11 (m, 1H), 4.38 (m, 1H), 7.22-7.33 (m, 2H), 7.9-7.98 (m, 2H).

後処理

  1. dissolutionDissolve
  2. customthe reaction
  3. customSeparate the phases
  4. extractionextract the aqueous phase with ethyl acetate
  5. washWash the combined organic layers with aqueous saturated sodium chloride
  6. dry with materialdry over anhydrous sodium sulfate
  7. filtrationfilter
  8. concentrationconcentrate under reduced pressure
  9. customPurify the resulting residue by silica gel flash chromatography
  10. washeluting with 25-100% ethyl acetate
  11. customRecrystallize from dichloromethane and hexane

出典と根拠

ORDレコード
ord-ce5642a54e914473b03af3b7a4d38967
出典データセット
uspto-grants-2013_11
特許番号
US08592590B2

反応ノート

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