Hydrazine → Oxadiazole

HRID 1746143

Reaktionsgleichung

Reaktionsgleichung von HRID 1746143
COC(=O)[C:4]1[CH:9]=[C:8]([OH:10])[CH:7]=[N:6][CH:5]=1.Br[C:13]1[CH:17]=[CH:16][O:15][N:14]=1.[NH2:18][NH2:19].[CH2:20]([O:22]C(OCC)OCC)[CH3:21]>CO.O.C(OCC)(=O)C>[N:6]1[CH:5]=[CH:4][CH:9]=[C:8]([O:10][C:13]2[CH2:17][CH2:16][O:15][N:14]=2)[CH:7]=1.[O:22]1[CH:20]=[CH:21][N:19]=[N:18]1

Komponenten

9

Edukt 4

HCID 9321HydrazineHCID 31214Ethyl orthoformateHCID 354317Methyl 5-hydroxypyridine-3-carboxylateHCID 139338913-Bromo-1,2-oxazole

Produkt 2

HCID 10197612OxadiazoleHCID 668185323-(Pyridin-3-yloxy)-4,5-dihydroisoxazole

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

3-(pyridin-3-yloxy)-4,5-dihydroisoxazole I-228a and I-228b were prepared in 3 steps according to the following procedures: 5-hydroxynicotinic acid methyl ester is reacted with racemic bromoisoxazole I-75 using Method 5. The resulting methyl ester (1.0 equiv) is dissolved in methanol (0.08 M) after which hydrazine (50 equiv, 50% by weight in water) is added and the reaction is allowed to stir for 14 h. The reaction mixture is then concentrated under vacuum and used directly in the next step. Triethylorthoformate (8.0 equiv) is added and the reaction is sealed and heated to reflux for 14 h. The reaction is then transferred to a separatory funnel with excess ethyl acetate and water. The organic layer was washed water and brine, drive over sodium sulfate and concentrated under vacuum to provide crude material which was purified using flash silica gel chromatography (gradient ethyl acetate/hexanes) to provide the desired racemic oxadiazole I-228. These compounds can be separated using chiral HPLC methods known in the art. For example, see chiral HPLC Method disclosed herein. [M+H]+=407.5 m/z. Activity: A

Aufarbeitung

  1. additionis added
  2. concentrationThe reaction mixture is then concentrated under vacuum
  3. customthe reaction is sealed
  4. temperatureheated
  5. temperatureto reflux for 14 h
  6. washThe organic layer was washed water and brine, drive over sodium sulfate
  7. concentrationconcentrated under vacuum
  8. customto provide crude material which
  9. customwas purified

Quellen und Nachweise

ORD-Eintrag
ord-ca6e29a8d6c749a7bc5a1dc6435a30d2
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09149465B2

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