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Potassium Iodide → 5,6-Dimethoxy-3-{1-[1,3-dihydro-2-oxo-2H-benzimidazole-1-yl-propyl]-4-piperidyl}-1,2-benzisoxazole

HRID 223266
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HRID 223266 반응식
[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[O:9][N:8]=2)[CH2:3][CH2:2]1.Cl[CH2:17][CH2:18][CH2:19][N:20]1[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[NH:22][C:21]1=[O:29].[C:30](=[O:33])([O-])[O-].[Na+].[Na+].[I-].[K+].CC(C)C[C:41](=[O:43])C>O>[CH3:41][O:43][C:13]1[C:14]([O:33][CH3:30])=[CH:15][C:10]2[O:9][N:8]=[C:7]([CH:4]3[CH2:3][CH2:2][N:1]([CH2:17][CH2:18][CH2:19][N:20]4[C:24]5[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=5[NH:22][C:21]4=[O:29])[CH2:6][CH2:5]3)[C:11]=2[CH:12]=1
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참가 물질

7

반응물 5

HCID 4875Potassium IodideHCID 7909Methyl Isobutyl KetoneHCID 10340Sodium CarbonateHCID 18104191-(3-chloropropyl)-1,3-dihydro-2H-benzimidazol-2-oneHCID 130764363-(Piperidin-4-yl)benzo[d]isoxazole

생성물 1

HCID 130784095,6-Dimethoxy-3-{1-[1,3-dihydro-2-oxo-2H-benzimidazole-1-yl-propyl]-4-piperidyl}-1,2-benzisoxazole
수율 28.1%

시약·촉매·용매 1

HCID 962Water용매

실험 절차

A stirred mixture of 4.40 g of 5,6-dimethoxy-3-(4-piperidyl-1,2-benzisoxazole, 3.35 g of 1-(3-chloropropyl)-1,3-dihydro-2H-benzimidazole-2-one, 3.56 g of sodium carbonate, 300 ml of 4-methyl-2-pentanone and 0.20 g of potassium iodide was stirred at reflux for 6.0 hrs and stirred overnight at ambient temperature. The reaction mixture was poured into water (300 ml) and extracted with dichloromethane. The extract was dried over anhydrous magnesium sulfate and the solvent was removed in vacuo to yield an oil. The oil was purified by high pressure liquid chromatography (Waters Prep 500; two silica gel columns) using 5% methanol in dichloromethane as the eluent. The free base was dissolved in ether and a saturated hydrogen bromide/ether solution was added dropwise to precipitate the hydrobromide salt. The salt was filtered, washed with ether and recrystallized from toluene/ether to yield 2.50 g (28.1%) of the product, mp 147°-149°.

후처리

  1. temperatureat reflux for 6.0 hrs
  2. stirringstirred overnight at ambient temperature
  3. extractionextracted with dichloromethane
  4. dry with materialThe extract was dried over anhydrous magnesium sulfate
  5. customthe solvent was removed in vacuo
  6. customto yield an oil
  7. customThe oil was purified by high pressure liquid chromatography (Waters Prep 500; two silica gel columns)
  8. dissolutionThe free base was dissolved in ether
  9. additiona saturated hydrogen bromide/ether solution was added dropwise
  10. customto precipitate the hydrobromide salt
  11. filtrationThe salt was filtered
  12. washwashed with ether
  13. customrecrystallized from toluene/ether

출처 및 근거

ORD 기록
ord-49c1433a67364e91afdce06e10e1bb07
출처 데이터셋
uspto-grants-1982_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US04352811

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