Pyridine → 5-(N-isobutyloxycarbonyl-1,4-dihydro-4-pyridyl)-6-(4-fluoro-phenyl)-2,3-dihydroimidazo[2,1-b]thiazole

HRID 1381680Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1381680
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[N:14]([CH:15]=2)[CH2:13][CH2:12][S:11]3)=[CH:4][CH:3]=1.[N:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[OH-].[K+].[CH2:24]([O:28][C:29](Cl)=[O:30])[CH:25]([CH3:27])[CH3:26]>C(Cl)Cl.O.C(OCC)(=O)C.CCCCCC.CO>[CH2:24]([O:28][C:29]([N:16]1[CH:21]=[CH:20][CH:19]([C:15]2[N:14]3[C:10]([S:11][CH2:12][CH2:13]3)=[N:9][C:8]=2[C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[CH:18]=[CH:17]1)=[O:30])[CH:25]([CH3:27])[CH3:26]

Komponenten

8

Edukt 4

HCID 1049Pyridine2×HCID 14797Potassium HydroxideHCID 62365Isobutyl chloroformate2×HCID 136398976-(4-Fluorophenyl)-2,3-dihydroimidazo[2,1-b][1,3]thiazole

Produkt 1

HCID 144059615-(N-isobutyloxycarbonyl-1,4-dihydro-4-pyridyl)-6-(4-fluoro-phenyl)-2,3-dihydroimidazo[2,1-b]thiazole

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel2×HCID 21879739Ethyl acetate hexane methanolLösungsmittel

Versuchsvorschrift

6-(4-Fluorophenyl)-2,3-dihydroimidazo[2,1-b]-thiazole (10.0 g, 0.0456 mol) and 11 mol (0.136 mol) of pyridine (previously stirred over potassium hydroxide) were dissolved in 150 ml of methylene chloride. To this cooled solution (10°) was added 17.75 g (0.13 mol) of isobutylchloroformate in 20 ml of methylene chloride under a nitrogen atmosphere. During the addition, the reaction pot temperature was not allowed to rise past 10°. After the addition, the reddish-colored solution was stirred at ambient temperature for 1 hour then heated under reflux for an additional 15 minutes. Thin-layer chromatography (ethyl acetate/hexane/methanol, 15:1:0.1) detected the presence of starting material. An additional 2.13 g (27 mmol) of pyridine, followed by 3.67 g (27 mmol) of isobutyl chloroformate, was added to the reaction vessel. The solution was stirred at room temperature for 1 hour, then, heated to reflux for 15 minutes. Thin layer analysis at this time did not detect starting material. The reaction mixture was diluted with 200 ml of water and extracted with methylene chloride (3×100 ml). The organic layer was dried, then, concentrated to yield 16.0 (85%) of 5-(N-isobutyloxycarbonyl-1,4-dihydro-4-pyridyl)-6-(4-fluoro-phenyl)-2,3-dihydroimidazo[2,1-b]thiazole; m.p. 144°-146° (from acetone/hexane).

Aufarbeitung

  1. additionDuring the addition
  2. customto rise past 10°
  3. additionAfter the addition
  4. temperaturethen heated
  5. temperatureunder reflux for an additional 15 minutes
  6. additionwas added to the reaction vessel
  7. stirringThe solution was stirred at room temperature for 1 hour
  8. temperatureheated
  9. temperatureto reflux for 15 minutes
  10. extractionextracted with methylene chloride (3×100 ml)
  11. customThe organic layer was dried
  12. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-d5e1e889db9343dd85939bbbb6824a1d
Quelldatensatz
uspto-grants-1989_02
Patentnummer
US04803279

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